bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation
Authors: Xulu Kutlwano R. , Augustine Tanya N.
Published: April 2021

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.
PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology
Authors: Duclos Valentin , Iep Alex , Gomez Léa , Goldfarb Lucas , Besson Florent L.
Published: April 2021

PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice. In parallel, the integration of PET imaging with radionuclide therapy, also known as radiolabeled theranostics, has paved the way towards highly sensitive radionuclide-based precision medicine, with major breakthroughs emerging in neuroendocrine tumors and prostate cancer. PET imaging of tumor immunity and beyond is also emerging, emphasizing the unique capabilities of PET molecular imaging to constantly adapt to emerging oncological challenges. However, these new horizons face the growing complexity of multidimensional data. In the era of precision medicine, statistical and computer sciences are currently revolutionizing image-based decision making, paving the way for more holistic cancer molecular imaging analyses at the whole-body level.
Structural and Functional Remodeling of Mitochondria in Cardiac Diseases
Authors: Sun Xiaonan , Alford Jalen , Qiu Hongyu
Published: April 2021

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.
SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus
Authors: Kawahara Kyoko , Mukai Tomoyuki , Iseki Masanori , Nagasu Akiko , Nagasu Hajime , Akagi Takahiko , Tsuji Shoko , Hiramatsu-Asano Sumie , Ueki Yasuyoshi , Ishihara Katsuhiko , Kashihara Naoki , Morita Yoshitaka
Published: April 2021

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Faslpr/lpr mice. Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220+CD4−CD8− T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.
The Neutrophil Secretome as a Crucial Link between Inflammation and Thrombosis
Authors: Blanch-Ruiz María Amparo , Ortega-Luna Raquel , Martínez-Cuesta María Ángeles , Álvarez Ángeles
Published: April 2021

Cardiovascular diseases are a leading cause of death. Blood–cell interactions and endothelial dysfunction are fundamental in thrombus formation, and so further knowledge of the pathways involved in such cellular crosstalk could lead to new therapeutical approaches. Neutrophils are secretory cells that release well-known soluble inflammatory signaling mediators and other complex cellular structures whose role is not fully understood. Studies have reported that neutrophil extracellular vesicles (EVs) and neutrophil extracellular traps (NETs) contribute to thrombosis. The objective of this review is to study the role of EVs and NETs as key factors in the transition from inflammation to thrombosis. The neutrophil secretome can promote thrombosis due to the presence of different factors in the EVs bilayer that can trigger blood clotting, and to the release of soluble mediators that induce platelet activation or aggregation. On the other hand, one of the main pathways by which NETs induce thrombosis is through the creation of a scaffold to which platelets and other blood cells adhere. In this context, platelet activation has been associated with the induction of NETs release. Hence, the structure and composition of EVs and NETs, as well as the feedback mechanism between the two processes that causes pathological thrombus formation, require exhaustive analysis to clarify their role in thrombosis.
Quantitative Proteomics Reveals the Dynamic Regulation of the Tomato Proteome in Response to Phytophthora infestans
Authors: Fan Kai-Ting , Hsu Yang , Yeh Ching-Fang , Chang Chi-Hsin , Chang Wei-Hung , Chen Yet-Ran
Published: April 2021

Late blight (LB) disease is a major threat to potato and tomato production. It is caused by the hemibiotrophic pathogen, Phytophthora infestans. P. infestans can destroy all of the major organs in plants of susceptible crops and result in a total loss of productivity. At the early pathogenesis stage, this hemibiotrophic oomycete pathogen causes an asymptomatic biotrophic infection in hosts, which then progresses to a necrotrophic phase at the later infection stage. In this study, to examine how the tomato proteome is regulated by P. infestans at different stages of pathogenesis, a data-independent acquisition (DIA) proteomics approach was used to trace the dynamics of the protein regulation. A comprehensive picture of the regulation of tomato proteins functioning in the immunity, signaling, defense, and metabolism pathways at different stages of P. infestans infection is revealed. Among the regulated proteins, several involved in mediating plant defense responses were found to be differentially regulated at the transcriptional or translational levels across different pathogenesis phases. This study increases understanding of the pathogenesis of P. infestans in tomato and also identifies key transcriptional and translational events possibly targeted by the pathogen during different phases of its life cycle, thus providing novel insights for developing a new strategy towards better control of LB disease in tomato.
COVID-19: Direct and Indirect Mechanisms of Statins
Authors: Pawlos Agnieszka , Niedzielski Mateusz , Gorzelak-Pabiś Paulina , Broncel Marlena , Woźniak Ewelina
Published: April 2021

The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-β and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.
Transcriptome Profiling of Cucumber (Cucumis sativus L.) Early Response to Pseudomonas syringae pv. lachrymans
Authors: Słomnicka Renata , Olczak-Woltman Helena , Sobczak Mirosław , Bartoszewski Grzegorz
Published: April 2021

Bacterial angular leaf spot disease (ALS) caused by Pseudomonas syringae pv. lachrymans (Psl) is one of the biological factors limiting cucumber open-field production. The goal of this study was to characterize cytological and transcriptomic response of cucumber to this pathogen. Plants of two inbred lines, B10 (susceptible) and Gy14 (resistant), were grown, and leaves were inoculated with highly virulent Psl strain 814/98 under growth chamber conditions. Microscopic and transcriptional evaluations were performed at three time points: before, 1 and 3 days post inoculation (dpi). Investigated lines showed distinct response to Psl. At 1 dpi bacterial colonies were surrounded by necrotized mesophyll cells. At 3 dpi, in the susceptible B10 line bacteria were in contact with degraded cells, whereas cells next to bacteria in the resistant Gy14 line were plasmolyzed, but apparently still alive and functional. Additionally, the level of H2O2 production was higher in resistant Gy14 plants than in B10 at both examined time points. In RNA sequencing more than 18,800 transcripts were detected in each sample. As many as 1648 and 2755 differentially expressed genes (DEGs) at 1 dpi as well as 2992 and 3141 DEGs at 3 dpi were identified in B10 and Gy14, respectively. DEGs were characterized in terms of functional categories. Resistant line Gy14 showed massive transcriptomic response to Psl at 1 dpi compared to susceptible line B10, while a similar number of DEGs was detected for both lines at 3 dpi. This suggests that dynamic transcriptomic response to the invading pathogen may be related with host resistance. This manuscript provides the first transcriptomic data on cucumber infected with the pathovar lachrymans and helps to elucidate resistance mechanism against ALS disease.
Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, Thrombotic Microangiopathy and ANCA-Vasculitis
Authors: Mazzariol Martina , Camussi Giovanni , Brizzi Maria Felice
Published: April 2021

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.
Molecular Chaperones and Thyroid Cancer
Authors: Paladino Letizia , Vitale Alessandra , Santonocito Radha , Pitruzzella Alessandro , Cipolla Calogero , Graceffa Giuseppa , Bucchieri Fabio , Conway de Macario Everly , Macario Alberto , Rappa Francesca
Published: April 2021

Thyroid cancers are the most common of the endocrine system malignancies and progress must be made in the areas of differential diagnosis and treatment to improve patient management. Advances in the understanding of carcinogenic mechanisms have occurred in various fronts, including studies of the chaperone system (CS). Components of the CS are found to be quantitatively increased or decreased, and some correlations have been established between the quantitative changes and tumor type, prognosis, and response to treatment. These correlations provide the basis for identifying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of the CS in tumorigenesis. Here, we discuss studies of the CS components in various thyroid cancers (TC). The chaperones belonging to the families of the small heat-shock proteins Hsp70 and Hsp90 and the chaperonin of Group I, Hsp60, have been quantified mostly by immunohistochemistry and Western blot in tumor and normal control tissues and in extracellular vesicles. Distinctive differences were revealed between the various thyroid tumor types. The most frequent finding was an increase in the chaperones, which can be attributed to the augmented need for chaperones the tumor cells have because of their accelerated metabolism, growth, and division rate. Thus, chaperones help the tumor cell rather than protect the patient, exemplifying chaperonopathies by mistake or collaborationism. This highlights the need for research on chaperonotherapy, namely the development of means to eliminate/inhibit pathogenic chaperones.
Genome-Wide Identification and Expression Patterns of the C2H2-Zinc Finger Gene Family Related to Stress Responses and Catechins Accumulation in Camellia sinensis [L.] O. Kuntze
Authors: Zhang Shiyang , Liu Junjie , Zhong Guixian , Wang Bo
Published: April 2021

The C2H2-zinc finger protein (C2H2-ZFP) is essential for the regulation of plant development and widely responsive to diverse stresses including drought, cold and salt stress, further affecting the late flavonoid accumulation in higher plants. Tea is known as a popular beverage worldwide and its quality is greatly dependent on the physiological status and growing environment of the tea plant. To date, the understanding of C2H2-ZFP gene family in Camellia sinensis [L.] O. Kuntze is not yet available. In the present study, 134 CsC2H2-ZFP genes were identified and randomly distributed on 15 chromosomes. The CsC2H2-ZFP gene family was classified into four clades and gene structures and motif compositions of CsC2H2-ZFPs were similar within the same clade. Segmental duplication and negative selection were the main forces driving the expansion of the CsC2H2-ZFP gene family. Expression patterns suggested that CsC2H2-ZFPs were responsive to different stresses including drought, salt, cold and methyl jasmonate (MeJA) treatment. Specially, several C2H2-ZFPs showed a significant correlation with the catechins content and responded to the MeJA treatment, which might contribute to the tea quality and specialized astringent taste. This study will lay the foundations for further research of C2H2-type zinc finger proteins on the stress responses and quality-related metabolites accumulation in C. sinensis.
Multi–Omics Analysis of Key microRNA–mRNA Metabolic Regulatory Networks in Skeletal Muscle of Obese Rabbits
Authors: Li Yanhong , Wang Jie , Elzo Mauricio A. , Gan Mingchuan , Tang Tao , Shao Jiahao , Lai Tianfu , Ma Yuan , Jia Xianbo , Lai Songjia
Published: April 2021

microRNAs (miRNAs), small non-coding RNA with a length of about 22 nucleotides, are involved in the energy metabolism of skeletal muscle cells. However, their molecular mechanism of metabolism in rabbit skeletal muscle is still unclear. In this study, 16 rabbits, 8 in the control group (CON–G) and 8 in the experimental group (HFD–G), were chosen to construct an obese model induced by a high–fat diet fed from 35 to 70 days of age. Subsequently, 54 differentially expressed miRNAs, 248 differentially expressed mRNAs, and 108 differentially expressed proteins related to the metabolism of skeletal muscle were detected and analyzed with three sequencing techniques (small RNA sequencing, transcriptome sequencing, and tandem mass tab (TMT) protein technology). It was found that 12 miRNAs and 12 core genes (e.g., CRYL1, VDAC3 and APIP) were significantly different in skeletal muscle from rabbits in the two groups. The network analysis showed that seven miRNA-mRNA pairs were involved in metabolism. Importantly, two miRNAs (miR-92a-3p and miR-30a/c/d-5p) regulated three transcription factors (MYBL2, STAT1 and IKZF1) that may be essential for lipid metabolism. These results enhance our understanding of molecular mechanisms associated with rabbit skeletal muscle metabolism and provide a basis for future studies in the metabolic diseases of human obesity.
Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model
Authors: Penna Claudia , Femminò Saveria , Caldera Fabrizio , Rubin Pedrazzo Alberto , Cecone Claudio , Alfì Edoardo , Comità Stefano , Higashiyama Takanobu , Trotta Francesco , Pagliaro Pasquale , Cavalli Roberta
Published: April 2021

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O2-CNN), and compared them with nitrogen CNN (N2-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O2, 5% CO2 and 74% N2) and their protective effects during hypoxia (1% O2, 5% CO2 and 94% N2) and reoxygenation (21% O2, 5% CO2 and 74% N2) were studied. Neither O2-CNN nor N2-CNN has any effect on the growth curve during normoxia. However, O2-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N2-CNN. O2-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.
Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells
Authors: Liu Yen-Tze , Ho Hsin-Yu , Lin Chia-Chieh , Chuang Yi-Ching , Lo Yu-Sheng , Hsieh Ming-Ju , Chen Mu-Kuan
Published: April 2021

Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.
Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies
Authors: Olinski Ryszard , Slupphaug Geir , Foksinski Marek , Krokan Hans Einar
Published: April 2021

DNA of all living cells undergoes continuous structural and chemical alterations resulting from fundamental cellular metabolic processes and reactivity of normal cellular metabolites and constituents. Examples include enzymatically oxidized bases, aberrantly methylated bases, and deaminated bases, the latter largely uracil from deaminated cytosine. In addition, the non-canonical DNA base uracil may result from misincorporated dUMP. Furthermore, uracil generated by deamination of cytosine in DNA is not always damage as it is also an intermediate in normal somatic hypermutation (SHM) and class shift recombination (CSR) at the Ig locus of B-cells in adaptive immunity. Many of the modifications alter base-pairing properties and may thus cause replicative and transcriptional mutagenesis. The best known and most studied epigenetic mark in DNA is 5-methylcytosine (5mC), generated by a methyltransferase that uses SAM as methyl donor, usually in CpG contexts. Oxidation products of 5mC are now thought to be intermediates in active demethylation as well as epigenetic marks in their own rights. The aim of this review is to describe the endogenous processes that surround the generation and removal of the most common types of DNA nucleobase modifications, namely, uracil and certain epigenetic modifications, together with their role in the development of hematological malignances. We also discuss what dictates whether the presence of an altered nucleobase is defined as damage or a natural modification.
TILLING-by-Sequencing+ to Decipher Oil Biosynthesis Pathway in Soybeans: A New and Effective Platform for High-Throughput Gene Functional Analysis
Authors: Lakhssassi Naoufal , Zhou Zhou , Cullen Mallory A. , Badad Oussama , El Baze Abdelhalim , Chetto Oumaima , Embaby Mohamed G. , Knizia Dounya , Liu Shiming , Neves Leandro G. , Meksem Khalid
Published: April 2021

Reverse genetic approaches have been widely applied to study gene function in crop species; however, these techniques, including gel-based TILLING, present low efficiency to characterize genes in soybeans due to genome complexity, gene duplication, and the presence of multiple gene family members that share high homology in their DNA sequence. Chemical mutagenesis emerges as a genetically modified-free strategy to produce large-scale soybean mutants for economically important traits improvement. The current study uses an optimized high-throughput TILLING by target capture sequencing technology, or TILLING-by-Sequencing+ (TbyS+), coupled with universal bioinformatic tools to identify population-wide mutations in soybeans. Four ethyl methanesulfonate mutagenized populations (4032 mutant families) have been screened for the presence of induced mutations in targeted genes. The mutation types and effects have been characterized for a total of 138 soybean genes involved in soybean seed composition, disease resistance, and many other quality traits. To test the efficiency of TbyS+ in complex genomes, we used soybeans as a model with a focus on three desaturase gene families, GmSACPD, GmFAD2, and GmFAD3, that are involved in the soybean fatty acid biosynthesis pathway. We successfully isolated mutants from all the six gene family members. Unsurprisingly, most of the characterized mutants showed significant changes either in their stearic, oleic, or linolenic acids. By using TbyS+, we discovered novel sources of soybean oil traits, including high saturated and monosaturated fatty acids in addition to low polyunsaturated fatty acid contents. This technology provides an unprecedented platform for highly effective screening of polyploid mutant populations and functional gene analysis. The obtained soybean mutants from this study can be used in subsequent soybean breeding programs for improved oil composition traits.
Impact of Medium-Sized Extracellular Vesicles on the Transduction Efficiency of Adeno-Associated Viruses in Neuronal and Primary Astrocyte Cell Cultures
Authors: Kovács Orsolya Tünde , Soltész-Katona Eszter , Marton Nikolett , Baricza Eszter , Hunyady László , Turu Gábor , Nagy György
Published: April 2021

(1) Adeno-associated viruses (AAV) are safe and efficient gene therapy vectors with promising results in the treatment of several diseases. Extracellular vesicles (EV) are phospholipid bilayer-surrounded structures carrying several types of lipids, proteins, and nucleic acids with the ability to cross biological barriers. EV-associated AAVs might serve as new and efficient gene therapy vectors considering that they carry the benefits of both AAVs and EVs. (2) We tested vesicle-associated AAVs and vesicles mixed with AAVs on two major cell types of the central nervous system: a neural cell line (N2A) and primary astrocyte cells. (3) In contrast to previously published in vivo observations, the extracellular vesicle packaging did not improve but, in the case of primary astrocyte cells, even inhibited the infection capacity of the AAV particles. The observed effect was not due to the inhibitory effects of the vesicles themselves, since mixing the AAVs with extracellular vesicles did not change the effectiveness. (4) Our results suggest that improvement of the in vivo efficacy of the EV-associated AAV particles is not due to the enhanced interaction between the AAV and the target cells, but most likely to the improved delivery of the AAVs through tissue barriers and to the shielding of AAVs from neutralizing antibodies.
Decreased Lymphangiogenic Activities and Genes Expression of Cord Blood Lymphatic Endothelial Progenitor Cells (VEGFR3+/Pod+/CD11b+ Cells) in Patient with Preeclampsia
Authors: Kwon Hayan , Kwon Ja-Young , Song Jeeun , Maeng Yong-Sun
Published: April 2021

The abnormal development or disruption of the lymphatic vasculature has been implicated in metabolic and hypertensive diseases. Recent evidence suggests that the offspring exposed to preeclampsia (PE) in utero are at higher risk of long-term health problems, such as cardiovascular and metabolic diseases in adulthood, owing to in utero fetal programming. We aimed to investigate lymphangiogenic activities in the lymphatic endothelial progenitor cells (LEPCs) of the offspring of PE. Human umbilical cord blood LEPCs from pregnant women with severe PE (n = 10) and gestationally matched normal pregnancies (n = 10) were purified with anti-vascular endothelial growth factor receptor 3 (VEGFR3)/podoplanin/CD11b microbeads using a magnetic cell sorter device. LEPCs from PE displayed significantly delayed differentiation and reduced formation of lymphatic endothelial cell (LEC) colonies compared with the LEPCs from normal pregnancies. LECs differentiated from PE-derived LEPCs exhibited decreased tube formation, migration, proliferation, adhesion, wound healing, and 3D-sprouting activities as well as increased lymphatic permeability through the disorganization of VE-cadherin junctions, compared with the normal pregnancy-derived LECs. In vivo, LEPCs from PE showed significantly reduced lymphatic vessel formation compared to the LEPCs of the normal pregnancy. Gene expression analysis revealed that compared to the normal pregnancy-derived LECs, the PE-derived LECs showed a significant decrease in the expression of pro-lymphangiogenic genes (GREM1, EPHB3, VEGFA, AMOT, THSD7A, ANGPTL4, SEMA5A, FGF2, and GBX2). Collectively, our findings demonstrate, for the first time, that LEPCs from PE have reduced lymphangiogenic activities in vitro and in vivo and show the decreased expression of pro-lymphangiogenic genes. This study opens a new avenue for investigation of the molecular mechanism of LEPC differentiation and lymphangiogenesis in the offspring of PE and subsequently may impact the treatment of long-term health problems such as cardiovascular and metabolic disorders of offspring with abnormal development of lymphatic vasculature.
Information Behavior on Video on Demand Services: User Motives and Their Selection Criteria for Content
Authors: Gutzeit Jennifer , Dorsch Isabelle , Stock Wolfgang G.
Published: April 2021

Introduction. Are viewers of video-on-demand (VoD) services more intrinsically (i.e., preferentially self-determined) or extrinsically (i.e., externally determined) motivated when selecting movies and series? For extrinsic motivation, we distinguish between algorithmically generated suggestions from the services and personal recommendations from other users. Methods. We empirically investigated the information behavior on video streaming services of users from German-speaking countries with the help of an online survey (N = 1258). Results. Active VoD users watch videos online mainly on a daily basis. They are externally determined in the selection of their videos both by algorithmically generated recommendations from the systems and―to a higher extent―from personal suggestions from acquaintances, friends, and relatives. However, there is a clear indication that intrinsic motivation plays a major role in the selection of videos. Discussion. Users of VoD services move in a cycle between machine-generated recommendations, suggestions, and exchange of opinions from and with other people, and self-determined information behavior.
The Nature of Employee–Organization Relationships at Polish Universities under Pandemic Conditions
Authors: Staniec Iwona
Published: April 2021

(1) Background: The aim of this study is to describe manager–employee and employee–employee relations during the COVID-19 pandemic and their impact on measures of the likely use of elements of remote teaching by university employees in the future. (2) Methods: The study used a descriptive-correlation research design with a survey as the primary instrument for data gathering. A total of 732 personnel took part in the survey, selected by a convenience sampling technique. The researchers used an adapted and modified instrument to gather data. The instrument underwent a reliability test. This study used structural equation modeling to confirm hypotheses. (3) Results: It was shown that manager–employee relations at Polish universities during the COVID-19 pandemic were of low quality. However, employee–employee relations were of above-average quality, and have a significant positive impact on intentions to use elements of remote working in the future. (4) Conclusions: Based on the results of the study, some general recommendations are presented for change management and relationship-building.
The Effect of Santolina chamaecyparissus and Tagetes patula Essential Oils on Biochemical Markers of Oxidative Stress in Aphids
Authors: Czerniewicz Paweł , Chrzanowski Grzegorz
Published: April 2021

This study investigated the toxicity of essential oils (EOs) from Santolina chamaecyparissus (L.) and Tagetes patula (L.) towards the green peach aphid Myzus persicae (Sulzer) and the bird cherry-oat aphid Rhopalosiphum padi (L.). The effects of the EOs on aphid population parameters and levels of biochemical markers of oxidative stress within insect tissues were analyzed. In laboratory bioassays, application of the studied EOs at sublethal concentrations reduced daily fecundity and led to a decrease in the intrinsic rate of natural increase in both aphid species. Treatment with EOs also induced generation of reactive oxygen species (ROS) within aphid tissues. The highest levels of superoxide anion and hydrogen peroxide were noted after 24 and 48 h of exposure. Moreover, a significant increase in lipid peroxidation was shown in treated aphids, especially between 48 and 72 h after exposure. The increase was more pronounced after treatment with the essential oil of S. chamaecyparissus, which also exhibited higher aphicidal activity in toxicity tests. The activities of antioxidant enzymes—superoxide dismutase (SOD) and catalase (CAT)—were significantly elevated in both aphid species in response to the tested EOs. The obtained results suggest that oxidative stress evoked by treatment with the studied EOs may be an important factor determining their toxicity towards aphids.
Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis
Authors: Nomura Kei , Ishikawa Dai , Okahara Koki , Ito Shoko , Haga Keiichi , Takahashi Masahito , Arakawa Atsushi , Shibuya Tomoyoshi , Osada Taro , Kuwahara-Arai Kyoko , Kirikae Teruo , Nagahara Akihito
Published: April 2021

Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger’s clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = −0.71, p = 2 × 10−9). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.
Evidence Map of Cupping Therapy
Authors: Choi Tae Young , Ang Lin , Ku Boncho , Jun Ji Hee , Lee Myeong Soo
Published: April 2021

This study aimed to describe and assess the current evidence in systematic reviews on cupping therapy for various conditions. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure, and six Korean databases for systematic reviews of trials on cupping treatments for any condition published prior to March 2021. We used a bubble plot to graphically display the clinical topics, the number of articles, the number of participants in the total population, confidence, and effectiveness. Thirteen systematic reviews that met the inclusion criteria were included in the evidence map, and 16 bubbles were created. The findings from six reviews showed potential benefits of cupping for conditions such as low back pain, ankylosing spondylitis, knee osteoarthritis, neck pain, herpes zoster, migraine, plaque psoriasis, and chronic urticaria. Cupping has been applied in a variety of clinical areas, and systematic reviews in a few of these areas have demonstrated statistically significant benefits. The evidence map provides a visual overview of cupping research volume and findings. Evidence mapping can facilitate the transfer of knowledge from researchers to policymakers and promote research on musculoskeletal pain (such as low back pain, neck pain, and knee osteoarthritis) and skin disease (plaque psoriasis).
Impact of Age and Comorbidity on Multimodal Management and Survival from Colorectal Cancer: A Population-Based Study
Authors: Kellokumpu Ilmo , Kairaluoma Matti , Mecklin Jukka-Pekka , Kellokumpu Henrik , Väyrynen Ville , Wirta Erkki-Ville , Sihvo Eero , Kuopio Teijo , Seppälä Toni T.
Published: April 2021

This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0–2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I–IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p < 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC.
Association of Guideline-Based Medical Therapy with Malignant Arrhythmias and Mortality among Heart Failure Patients Implanted with Cardioverter Defibrillator (ICD) or Cardiac Resynchronization-Defibrillator Device (CRTD)
Authors: Hasin Tal , Davarashvili Ilia , Michowitz Yoav , Farkash Rivka , Presman Haya , Glikson Michael , Rav-Acha Moshe
Published: April 2021

Aim: Evaluate prevalence of heart failure (HF) medications and their association with ventricular arrhythmia (VA) and survival among patients implanted with primary prevention implantable cardiac defibrillator (ICD)/cardiac resynchronization therapy + defibrillator (CRTD) devices. Methods: Association of treatment and dose (% guideline recommended target) of beta-adrenergic receptor antagonist (BB), angiotensin-antagonists (AngA), and mineralocorticoid-antagonists (MRA), after ICD/CRTD implant with VA and mortality was retrospectively analyzed. Results: Study included 186 HF patients; 42.5% and 57.5% implanted with ICD and CRTD, respectively. During 3.8 (2.1;6.7) years; 52 (28%) had VA and 77 (41.4%) died. Treatment (% of patients) included: BB (83%), AngA (87%), and MRA (59%). Median doses were 25(12.5;50)% of target for all medications. BB treatment >25% target dose was associated with reduced VA incidence. In the multivariable model including age, gender, diabetes, heart rate, and medication doses, increased BB dose was associated with reduced VA (hazard ratio (HR) 0.443 95% CI 0.222–0.885; p = 0.021). In the multivariable model for overall mortality including age, gender, renal disease, VA, and medical treatment, VA was associated with increased mortality (HR 2.672; 95% CI 1.429–4.999; p = 0.002) and AngA treatment was associated with reduced mortality (HR 0.515; 95% CI 0.285–0.929; p = 0.028). Conclusions: In this cohort of real-life HF patients discharged after ICD/CRTD implant, prevalence of guideline-based HF medications was high, albeit with low doses. Higher BB dose was associated with reduced VA, while AngA was associated with improved survival.
Time Is Brain: Acute Control of Repetitive Seizures and Status Epilepticus Using Alternative Routes of Administration of Benzodiazepines
Authors: Almohaish Sulaiman , Sandler Melissa , Brophy Gretchen M.
Published: April 2021

Time plays a major role in seizure evaluation and treatment. Acute repetitive seizures and status epilepticus are medical emergencies that require immediate assessment and treatment for optimal therapeutic response. Benzodiazepines are considered the first-line agent for rapid seizure control. Thus, various routes of administration of benzodiazepines have been studied to facilitate a quick, effective, and easy therapy administration. Choosing the right agent may vary based on the drug and route properties, patient’s environment, caregiver’s skills, and drug accessibility. The pharmacokinetic and pharmacodynamic aspects of benzodiazepines are essential in the decision-making process. Ultimately, agents and routes that give the highest bioavailability, fastest absorption, and a modest duration are preferred. In the outpatient setting, intranasal and buccal routes appear to be equally effective and more rapidly administered than rectal diazepam. On the other hand, in the inpatient setting, if available, the IV route is ideal for benzodiazepine administration to avoid any potential absorption delay. In this article, we will provide an overview and comparison of the various routes of benzodiazepine administration for acute control of repetitive seizures and status epilepticus.
Precision Phenomapping of Acute Coronary Syndromes to Improve Patient Outcomes
Authors: Andreotti Felicita , Iervolino Adelaide , Navarese Eliano Pio , Maggioni Aldo Pietro , Crea Filippo , Scambia Giovanni
Published: April 2021

Acute coronary syndromes (ACS) are a global leading cause of death. These syndromes show heterogeneity in presentation, mechanisms, outcomes and responses to treatment. Precision medicine aims to identify and synthesize unique features in individuals, translating the acquired data into improved personalised interventions. Current precision treatments of ACS include immediate coronary revascularisation driven by ECG ST-segment elevation, early coronary angiography based on elevated blood cardiac troponins in patients without ST-segment elevation, and duration of intensified antithrombotic therapy according to bleeding risk scores. Phenotypically stratified analyses of multi-omic datasets are urgently needed to further refine and couple the diagnosis and treatment of these potentially life-threatening conditions. We provide definitions, examples and possible ways to advance precision treatments of ACS.
Trend and Geographic Disparities in the Mortality Rates of Primary Systemic Vasculitis in the United States from 1999 to 2019: A Population-Based Study
Authors: Rodriguez-Pla Alicia , Rossello-Urgell Jose
Published: April 2021

The current data on rates and geographic distribution of vasculitis mortality are limited. We aimed to estimate the mortality rates of primary systemic vasculitis and its geographic distribution using recent population data in the United States. The mortality rates of vasculitis from 1999 to 2019 were obtained from the Center for Disease Control (CDC) Wonder Multiple Cause of Death (MCD). The age-adjusted rates per million for vasculitis as MCD and as an underlying cause of death (UCD) were calculated by state using demographics. A joinpoint regression analysis was applied to evaluate trends over time. The age-adjusted mortality rate of vasculitis as MCD was 4.077 (95% CI: 4.029–4.125) and as a UCD was 1.888 per million (95% CI: 1.855–1.921). Since 1999, mortality rates have progressively decreased. The age-adjusted mortality rate was higher in females than in males. The highest mortality rate for vasculitis as MCD was in White patients (4.371; 95% CI: 4.317–4.424). The northern states and areas with lower populations had higher mortality rates. We found a trend of progressive decreases in the mortality rates of vasculitis, as well as gender, racial, and geographic disparities. Further analyses are warranted to better understand the factors associated with these disparities in order to implement targeted public health interventions to decrease them.