bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderate, but Not Excessive, Training Attenuates Autophagy Machinery in Metabolic Tissues
Authors: da Rocha Alisson L. , Pinto Ana P. , Morais Gustavo P. , Marafon Bruno B. , Rovina Rafael L. , Veras Allice S. C. , Teixeira Giovana R. , Pauli José R. , de Moura Leandro P. , Cintra Dennys E. , Ropelle Eduardo R. , Rivas Donato A. , da Silva Adelino S. R.
Published: November 2020

The protective effects of chronic moderate exercise-mediated autophagy include the prevention and treatment of several diseases and the extension of lifespan. In addition, physical exercise may impair cellular structures, requiring the action of the autophagy mechanism for clearance and renovation of damaged cellular components. For the first time, we investigated the adaptations on basal autophagy flux in vivo in mice’s liver, heart, and skeletal muscle tissues submitted to four different chronic exercise models: endurance, resistance, concurrent, and overtraining. Measuring the autophagy flux in vivo is crucial to access the functionality of the autophagy pathway since changes in this pathway can occur in more than five steps. Moreover, the responses of metabolic, performance, and functional parameters, as well as genes and proteins related to the autophagy pathway, were addressed. In summary, the regular exercise models exhibited normal/enhanced adaptations with reduced autophagy-related proteins in all tissues. On the other hand, the overtrained group presented higher expression of Sqstm1 and Bnip3 with negative morphological and physical performance adaptations for the liver and heart, respectively. The groups showed different adaptions in autophagy flux in skeletal muscle, suggesting the activation or inhibition of basal autophagy may not always be related to improvement or impairment of performance.
Neurodegeneration and Inflammation—An Interesting Interplay in Parkinson’s Disease
Authors: Marogianni Chrysoula , Sokratous Maria , Dardiotis Efthimios , Hadjigeorgiou Georgios M. , Bogdanos Dimitrios , Xiromerisiou Georgia
Published: November 2020

Parkinson’s disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut–brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.
FAK Signaling in Rhabdomyosarcoma
Authors: Perrone Clara , Pomella Silvia , Cassandri Matteo , Braghini Maria Rita , Pezzella Michele , Locatelli Franco , Rota Rossella
Published: November 2020

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges. It plays a role in cell motility, survival, and proliferation in response to integrin and growth factor receptors’ activation. FAK is often dysregulated in cancer, being upregulated and/or overactivated in several adult and pediatric tumor types. In RMS, both in vitro and preclinical studies point to a role of FAK in tumor cell motility/invasion and proliferation, which is inhibited by FAK inhibitors. In this review, we summarize the data on FAK expression and modulation in RMS. Moreover, we give an overview of the approaches to inhibit FAK in both preclinical and clinical cancer settings.
Experimental Animal Model Systems for Understanding Salivary Secretory Disorders
Authors: Kim Ji-Youn , An Chang-Hyeon , Kim Jae-Young , Jung Jae-Kwang
Published: November 2020

Salivary secretory disorders are life-disrupting pathologic conditions with a high prevalence, especially in the geriatric population. Both patients and clinicians frequently feel helpless and get frustrated by the currently available therapeutic strategies, which consist mainly of palliative managements. Accordingly, to unravel the underlying mechanisms and to develop effective and curative strategies, several animal models have been developed and introduced. Experimental findings from these models have contributed to answer biological and biomedical questions. This review aims to provide various methodological considerations used for the examination of pathological fundamentals in salivary disorders using animal models and to summarize the obtained findings. The information provided in this review could provide plausible solutions for overcoming salivary disorders and also suggest purpose-specific experimental animal systems.
Updates on the Risk of Neuropsychiatric and Gastrointestinal Comorbidities in Rosacea and Its Possible Relationship with the Gut–Brain–Skin Axis
Authors: Woo Yu Ri , Han Yu Jin , Kim Hei Sung , Cho Sang Hyun , Lee Jeong Deuk
Published: November 2020

Rosacea is a common chronic cutaneous inflammatory disorder. Recently, patients with rosacea were identified as having a higher risk of developing various comorbidities such as cardiovascular disease, psychiatric disorders, neurologic disorders, and gastrointestinal disorders. However, the risks of some comorbidities in patients with rosacea are somewhat contradictory, depending upon the study design. Moreover, pathomechanisms associated with the comorbidities of patients with rosacea remain poorly elucidated. The purpose of this review was to provide the most up-to-date evidence on the risks of neuropsychiatric and gastrointestinal comorbidities in patients with rosacea. Moreover, the molecular pathomechanisms associated with neuropsychiatric and gastrointestinal comorbidities in patients with rosacea were evaluated based on recent studies. This review was also intended to focus more on the role of the gut–brain–skin axis in the association of neuropsychiatric and gastrointestinal comorbidities in rosacea.
The Role of Age, Neutrophil Infiltration and Antibiotics Timing in the Severity of Streptococcus pneumoniae Pneumonia. Insights from a Multi-Level Mathematical Model Approach
Authors: Santos Guido , Vera Julio
Published: November 2020

Bacterial pneumonia is one of the most prevalent infectious diseases and has high mortality in sensitive patients (children, elderly and immunocompromised). Although an infection, the disease alters the alveolar epithelium homeostasis and hinders normal breathing, often with fatal consequences. A special case is hospitalized aged patients, which present a high risk of infection and death because of the community acquired version of the Streptococcus pneumoniae pneumonia. There is evidence that early antibiotics treatment decreases the inflammatory response during pneumonia. Here, we investigate mechanistically this strategy using a multi-level mathematical model, which describes the 24 first hours after infection of a single alveolus from the key signaling networks behind activation of the epithelium to the dynamics of the local immune response. With the model, we simulated pneumonia in aged and young patients subjected to different antibiotics timing. The results show that providing antibiotics to elderly patients 8 h in advance compared to young patients restores in aged individuals the effective response seen in young ones. This result suggests the use of early, probably prophylactic, antibiotics treatment in aged hospitalized people with high risk of pneumonia.
Sequence-Dependent Nanofiber Structures of Phenylalanine and Isoleucine Tripeptides
Authors: Xiong Qinsi , Liu Ziye , Han Wei
Published: November 2020

The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a result of insufficient understanding of the relationship between peptide sequence and assembled supramolecular structures. We report a hybrid-resolution model to computationally explore the sequence–structure relationship of self-assembly for tripeptides containing only phenylalanine and isoleucine. We found that all these tripeptides have a tendency to assemble into nanofibers composed of laterally associated filaments. Molecular arrangements within the assemblies are diverse and vary depending on the sequences. This structural diversity originates from (1) distinct conformations of peptide building blocks that lead to different surface geometries of the filaments and (2) unique sidechain arrangements at the filament interfaces for each sequence. Many conformations are available for tripeptides in solution, but only an extended β-strand and another resembling a right-handed turn are observed in assemblies. It was found that the sequence dependence of these conformations and the packing of resulting filaments are determined by multiple competing noncovalent forces, with hydrophobic interactions involving Phe being particularly important. The sequence pattern for each type of assembly conformation and packing has been identified. These results highlight the importance of the interplay between conformation, molecular packing, and sequences for determining detailed nanostructures of peptides and provide a detailed insight to support a more precise design of peptide-based nanomaterials.
Coenzyme Q10: Novel Formulations and Medical Trends
Authors: Pastor-Maldonado Carmen J. , Suárez-Rivero Juan M. , Povea-Cabello Suleva , Álvarez-Córdoba Mónica , Villalón-García Irene , Munuera-Cabeza Manuel , Suárez-Carrillo Alejandra , Talaverón-Rey Marta , Sánchez-Alcázar José A.
Published: November 2020

The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.
The Combination of the M2 Muscarinic Receptor Agonist and Chemotherapy Affects Drug Resistance in Neuroblastoma Cells
Authors: Lucianò Anna Maria , Perciballi Elisa , Fiore Mario , Del Bufalo Donatella , Tata Ada Maria
Published: November 2020

One of the major limits of chemotherapy is depending on the ability of the cancer cells to elude and adapt to different drugs. Recently, we demonstrated how the activation of the M2 muscarinic receptor could impair neuroblastoma cell proliferation. In the present paper, we investigate the possible effects mediated by the preferential M2 receptor agonist arecaidine propargyl ester (APE) on drug resistance in two neuroblastoma cell lines, SK-N-BE and SK-N-BE(2C), a sub-clone presenting drug resistance. In both cell lines, we compare the expression of the M2 receptor and the effects mediated by the M2 agonist APE on cell cycle, demonstrating a decreased percentage of cells in S phase and an accumulation of SK-N-BE cells in G1 phase, while the APE treatment of SK-N-BE(2C) cells induced a block in G2/M phase. The withdrawal of the M2 agonist from the medium shows that only the SK-N-BE(2C) cells are able to rescue cell proliferation. Further, we demonstrate that the co-treatment of low doses of APE with doxorubicin or cisplatin significantly counteracts cell proliferation when compared with the single treatment. Analysis of the expression of ATP-binding cassette (ABC) efflux pumps demonstrates the ability of the M2 agonist to downregulate their expression and that this negative modulation may be dependent on N-MYC decreased expression induced by the M2 agonist. Our data demonstrate that the combined effect of low doses of conventional drugs and the M2 agonist may represent a new promising therapeutic approach in neuroblastoma treatment, in light of its significant impact on drug resistance and the possible reduction in the side effects caused by high doses of chemotherapy drugs.
BDNF rs6265 Polymorphism and Its Methylation in Patients with Stroke Undergoing Rehabilitation
Authors: Santoro Massimo , Siotto Mariacristina , Germanotta Marco , Bray Elisa , Mastrorosa Alessia , Galli Camilla , Papadopoulou Dionysia , Aprile Irene
Published: November 2020

Brain-Derived Neurotrophic Factor (BDNF) and its rs6265 single nucleotide polymorphism (SNP) play an important role in post-stroke recovery. We investigated the correlation between BDNF rs6265 SNP and recovery outcome, measured by the modified Barthel index, in 49 patients with stroke hospitalized in our rehabilitation center at baseline (T0) and after 30 sessions of rehabilitation treatment (T1); moreover, we analyzed the methylation level of the CpG site created or abolished into BDNF rs6265 SNP. In total, 11 patients (22.4%) were heterozygous GA, and 32 (65.3%) and 6 (12.2%) patients were homozygous GG and AA, respectively. The univariate analysis showed a significant relationship between the BDNF rs6265 SNP and the modified Barthel index cut-off (χ2(1, N = 48) = 3.86, p = 0.049), considering patients divided for carrying (A+) or not carrying (A−) the A allele. A higher percentage of A− patients obtained a favorable outcome, as showed by the logistic regression model corrected by age and time since the stroke onset, compared with the A+ patients (OR: 5.59). At baseline (T0), the percentage of BDNF methylation was significantly different between GG (44.6 ± 1.1%), GA (39.5 ± 2.8%) and AA (28.5 ± 1.7%) alleles (p < 0.001). After rehabilitation (T1), only patients A− showed a significant increase in methylation percentages (mean change = 1.3, CI: 0.4–2.2, p = 0.007). This preliminary study deserves more investigation to confirm if BDNF rs6265 SNP and its methylation could be used as a biological marker of recovery in patients with stroke undergoing rehabilitation treatment.
Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects
Authors: Lee Kyung-Eun , Jeong Sugyeong , Yun Seok Kyun , Kyung Seoyeon , Sophie Abadie , Moh Sang Hyun , Seo Hyo Hyun , Park Myeong Sam , Kang Seunghyun , Yeo Hyeonju
Published: November 2020

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11β-HSD1.
Cell Type-Specific Adhesion and Migration on Laser-Structured Opaque Surfaces
Authors: Schaeske Jörn , Fadeeva Elena , Schlie-Wolter Sabrina , Deiwick Andrea , Chichkov Boris N. , Ingendoh-Tsakmakidis Alexandra , Stiesch Meike , Winkel Andreas
Published: November 2020

Cytocompatibility is essential for implant approval. However, initial in vitro screenings mainly include the quantity of adherent immortalized cells and cytotoxicity. Other vital parameters, such as cell migration and an in-depth understanding of the interaction between native tissue cells and implant surfaces, are rarely considered. We investigated different laser-fabricated spike structures using primary and immortalized cell lines of fibroblasts and osteoblasts and included quantification of the cell area, aspect ratio, and focal adhesions. Furthermore, we examined the three-dimensional cell interactions with spike topographies and developed a tailored migration assay for long-term monitoring on opaque materials. While fibroblasts and osteoblasts on small spikes retained their normal morphology, cells on medium and large spikes sank into the structures, affecting the composition of the cytoskeleton and thereby changing cell shape. Up to 14 days, migration appeared stronger on small spikes, probably as a consequence of adequate focal adhesion formation and an intact cytoskeleton, whereas human primary cells revealed differences in comparison to immortalized cell lines. The use of primary cells, analysis of the cell–implant structure interaction as well as cell migration might strengthen the evaluation of cytocompatibility and thereby improve the validity regarding the putative in vivo performance of implant material.
Can Gut Microbiota Affect Dry Eye Syndrome?
Authors: Moon Jayoon , Yoon Chang Ho , Choi Se Hyun , Kim Mee Kum
Published: November 2020

Using metagenomics, continuing evidence has elicited how intestinal microbiota trigger distant autoimmunity. Sjögren’s syndrome (SS) is an autoimmune disease that affects the ocular surface, with frequently unmet therapeutic needs requiring new interventions for dry eye management. Current studies also suggest the possible relation of autoimmune dry eye with gut microbiota. Herein, we review the current knowledge of how the gut microbiota interact with the immune system in homeostasis as well as its influence on rheumatic and ocular autoimmune diseases, and compare their characteristics with SS. Both rodent and human studies regarding gut microbiota in SS and environmental dry eye are explored, and the effects of prebiotics and probiotics on dry eye are discussed. Recent clinical studies have commonly observed a correlation between gut dysbiosis and clinical manifestations of SS, while environmental dry eye portrays characteristics in between normal and autoimmune. Moreover, a decrease in both the Firmicutes/Bacteroidetes ratio and genus Faecalibacterium have most commonly been observed in SS subjects. The presumable pathways forming the “gut dysbiosis–ocular surface–lacrimal gland axis” are introduced. This review may provide perspectives into the link between the gut microbiome and dry eye, enhance our understanding of the pathogenesis in autoimmune dry eye, and be useful in the development of future interventions.
Pygenic Acid A (PA) Sensitizes Metastatic Breast Cancer Cells to Anoikis and Inhibits Metastasis In Vivo
Authors: Lim Ga-Eun , Sung Jee Young , Yu Suyeun , Kim Younmi , Shim Jaegal , Kim Hyo Jung , Cho Myoung Lae , Lee Jae-Seon , Kim Yong-Nyun
Published: November 2020

Metastasis is the main cause of cancer-related deaths. Anoikis is a type of apoptosis caused by cell detachment, and cancer cells become anoikis resistant such that they survive during circulation and can successfully metastasize. Therefore, sensitization of cancer cells to anoikis could prevent metastasis. Here, by screening for anoikis sensitizer using natural compounds, we found that pygenic acid A (PA), a natural compound from Prunella vulgaris, not only induced apoptosis but also sensitized the metastatic triple-negative breast cancer cell lines, MDA-MB-231 cells (human) and 4T1 cells (mouse), to anoikis. Apoptosis protein array and immunoblotting analysis revealed that PA downregulated the pro-survival proteins, including cIAP1, cIAP2, and survivin, leading to cell death of both attached and suspended cells. Interestingly, PA decreased the levels of proteins associated with anoikis resistance, including p21, cyclin D1, p-STAT3, and HO-1. Ectopic expression of active STAT3 attenuated PA-induced anoikis sensitivity. Although PA activated ER stress and autophagy, as determined by increases in the levels of characteristic markers, such as IRE1α, p-elF2α, LC3B I, and LC3B II, PA treatment resulted in p62 accumulation, which could be due to PA-induced defects in autophagy flux. PA also decreased metastatic characteristics, such as cell invasion, migration, wound closure, and 3D growth. Finally, lung metastasis of luciferase-labeled 4T1 cells decreased following PA treatment in a syngeneic mouse model when compared with the control. These data suggest that PA sensitizes metastatic breast cancer cells to anoikis via multiple pathways, such as inhibition of pro-survival pathways and activation of ER stress and autophagy, leading to the inhibition of metastasis. These findings suggest that sensitization to anoikis by PA could be used as a new therapeutic strategy to control the metastasis of breast cancer.
Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-α and IL-17A Expression in Mucosal Inflammation
Authors: Appiah Michael G. , Park Eun Jeong , Darkwah Samuel , Kawamoto Eiji , Akama Yuichi , Gaowa Arong , Kalsan Manisha , Ahmad Shandar , Shimaoka Motomu
Published: November 2020

Sepsis is a systemic inflammatory disorder induced by a dysregulated immune response to infection resulting in dysfunction of multiple critical organs, including the intestines. Previous studies have reported contrasting results regarding the abilities of exosomes circulating in the blood of sepsis mice and patients to either promote or suppress inflammation. Little is known about how the gut epithelial cell-derived exosomes released in the intestinal luminal space during sepsis affect mucosal inflammation. To study this question, we isolated extracellular vesicles (EVs) from intestinal lavage of septic mice. The EVs expressed typical exosomal (CD63 and CD9) and epithelial (EpCAM) markers, which were further increased by sepsis. Moreover, septic-EV injection into inflamed gut induced a significant reduction in the messaging of pro-inflammatory cytokines TNF-α and IL-17A. MicroRNA (miRNA) profiling and reverse transcription and quantitative polymerase chain reaction (RT-qPCR) revealed a sepsis-induced exosomal increase in multiple miRNAs, which putatively target TNF-α and IL-17A. These results imply that intestinal epithelial cell (IEC)-derived luminal EVs carry miRNAs that mitigate pro-inflammatory responses. Taken together, our study proposes a novel mechanism by which IEC EVs released during sepsis transfer regulatory miRNAs to cells, possibly contributing to the amelioration of gut inflammation.
Investigating the Benefit of Combined Androgen Modulation and Hypofractionation in Prostate Cancer
Authors: Zamagni Alice , Zanoni Michele , Cortesi Michela , Arienti Chiara , Pignatta Sara , Naldini Antonella , Sarnelli Anna , Romeo Antonino , Tesei Anna
Published: November 2020

Hypofractionation is currently considered a valid alternative to conventional radiotherapy for the treatment of patients with organ-confined prostate cancer. Recent data have demonstrated that extreme hypofractionation, which involves the use of a high radiation dose per delivered fraction and concomitant reduction of sessions, is a safe and effective treatment, even though its radiobiological rationale is still lacking. The present work aims to investigate the biological basis sustaining this approach and to evaluate the potential of a hypofractionated regimen in combination with androgen deprivation therapy, one of the major standards of care for prostate cancer. Findings show that androgen receptor (AR) modulation, by use of androgens and antiandrogens, has a significant impact on cell survival, especially in hypoxic conditions (4% O2). Subsequent experiments have revealed that AR activity as a transcription factor is involved in the onset of malignant senescence-associated secretory phenotype (SASP) and activation of DNA repair cascade. In particular, we found that AR stimulation in hypoxic conditions promotes the enhanced transcription of ATM gene, the cornerstone kinase of the DNA damage repair genes. Together, these data provide new potential insights to justify the use of androgen deprivation therapy, in particular with second-generation anti-androgens such as enzalutamide, in combination with radiotherapy.
Negative Regulation of the Differentiation of Flk2− CD34− LSK Hematopoietic Stem Cells by EKLF/KLF1
Authors: Hung Chun-Hao , Wang Keh-Yang , Liou Yae-Huei , Wang Jing-Ping , Huang Anna Yu-Szu , Lee Tung-Liang , Jiang Si-Tse , Liao Nah-Shih , Shyu Yu-Chiau , Shen Che-Kun James
Published: November 2020

Erythroid Krüppel-like factor (EKLF/KLF1) was identified initially as a critical erythroid-specific transcription factor and was later found to be also expressed in other types of hematopoietic cells, including megakaryocytes and several progenitors. In this study, we have examined the regulatory effects of EKLF on hematopoiesis by comparative analysis of E14.5 fetal livers from wild-type and Eklf gene knockout (KO) mouse embryos. Depletion of EKLF expression greatly changes the populations of different types of hematopoietic cells, including, unexpectedly, the long-term hematopoietic stem cells Flk2− CD34− Lin− Sca1+ c-Kit+ (LSK)-HSC. In an interesting correlation, Eklf is expressed at a relatively high level in multipotent progenitor (MPP). Furthermore, EKLF appears to repress the expression of the colony-stimulating factor 2 receptor β subunit (CSF2RB). As a result, Flk2− CD34− LSK-HSC gains increased differentiation capability upon depletion of EKLF, as demonstrated by the methylcellulose colony formation assay and by serial transplantation experiments in vivo. Together, these data demonstrate the regulation of hematopoiesis in vertebrates by EKLF through its negative regulatory effects on the differentiation of the hematopoietic stem and progenitor cells, including Flk2− CD34− LSK-HSCs.
The Effect of Sodium Butyrate on Adventitious Shoot Formation Varies among the Plant Species and the Explant Types
Authors: Lee Myoung Hui , Lee Jiyoung , Choi Seung Hee , Jie Eun Yee , Jeong Jae Cheol , Kim Cha Young , Kim Suk Weon
Published: November 2020

Histone acetylation plays an important role in plant growth and development. Here, we investigated the effect of sodium butyrate (NaB), a histone deacetylase inhibitor, on adventitious shoot formation from protoplast-derived calli and cotyledon explants of tobacco (Nicotiana benthamiana) and tomato (Solanum lycopersicum). The frequency of adventitious shoot formation from protoplast-derived calli was higher in shoot induction medium (SIM) containing NaB than in the control. However, the frequency of adventitious shoot formation from cotyledon explants of tobacco under the 0.1 mM NaB treatment was similar to that in the control, but it decreased with increasing NaB concentration. Unlike in tobacco, NaB decreased adventitious shoot formation in tomato explants in a concentration-dependent manner, but it did not have any effect on adventitious shoot formation in calli. NaB inhibited or delayed the expression of D-type cyclin (CYCD3-1) and shoot-regeneration regulatory gene WUSCHEL (WUS) in cotyledon explants of tobacco and tomato. However, compared to that in control SIM, the expression of WUS was promoted more rapidly in tobacco calli cultured in NaB-containing SIM, but the expression of CYCD3-1 was inhibited. In conclusion, the effect of NaB on adventitious shoot formation and expression of CYCD3-1 and WUS genes depended on the plant species and whether the effects were tested on explants or protoplast-derived calli.
The Role of Chemokines in the Development of Gastric Cancer—Diagnostic and Therapeutic Implications
Authors: Pawluczuk Elzbieta , Łukaszewicz-Zając Marta , Mroczko Barbara
Published: November 2020

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC.
Higher Disease and Pain Severity and Fatigue and Lower Balance Skills Are Associated with Higher Prevalence of Falling among Individuals with the Inflammatory Disease of Neuromyelitis Optica Spectrum Disorder (NMOSD)
Authors: Barzegar Mahdi , Sadeghi Bahmani Dena , Mirmosayyeb Omid , Azarbayejani Reyhaneh , Afshari-Safavi Alireza , Vaheb Saeed , Nehzat Nasim , Dana Afshin , Shaygannejad Vahid , Motl Robert W. , Brand Serge
Published: November 2020

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory and autoimmune disorder that is associated with impaired vision, sensory loss, pain, fatigue, and spasms in the upper and lower limbs. Typically, persons with this disorder are also at higher risks of falls. Given this, the aims of the study were to compare the prevalence rates of falling for NMOSD cases and healthy controls (HCs), and to predict falling in the former group based on sociodemographic, psychological, and illness-related factors. Method: A total of 95 adults with NMOSD (Mean age = 34.89 years; 70.5% females) and 100 matched HCs took part in the study. All participants completed a series of questionnaires covering sociodemographic information and falling rates. The NMOSD individuals also reported on disease duration, pain, fatigue, and fear of falling, while their balance performance was objectively assessed. Results: Compared to healthy controls, the NMOSD cases had a 2.5-fold higher risk of falling. In this latter group, higher scores for pain, fatigue, fear of falling, and higher EDSS scores were distinguished between fallers and non-fallers, and objective balance skills had no predictive value. Conclusions: Compared to healthy controls, NMOSD sufferers had a 2.5-fold higher risk of experiencing falls. In this group, disease impairments (EDSS, fatigue, pain) predicted falling. Specific interventions such as regular resistance training might reduce the risk of falling.
The Role of Cardiovascular Imaging in the Evaluation of Rheumatic and Neuromuscular Disorders
Authors: Mavrogeni Sophie I.
Published: November 2020

Autoimmune rheumatic diseases (ARD) and neuromuscular disorders can affect a number of organs [...]
Laryngopharyngeal Reflux: A State-of-the-Art Algorithm Management for Primary Care Physicians
Authors: Lechien Jerome R. , Saussez Sven , Muls Vinciane , Barillari Maria R. , Chiesa-Estomba Carlos M. , Hans Stéphane , Karkos Petros D.
Published: November 2020

Laryngopharyngeal reflux (LPR) is a common disease in the general population with acute or chronic symptoms. LPR is often misdiagnosed in primary care because of the lack of typical gastroesophageal reflux disease (GERD) symptoms and findings on endoscopy. Depending on the physician’s specialty and experience, LPR may be over- or under-diagnosed. Management of LPR is potentially entirely feasible in primary care as long as General Practitioners (GPs) are aware of certain “red flags” that will prompt referral to a Gastroenterologist or an Otolaryngologist. The use of patient-reported outcome questionnaires and the consideration of some easy ways to diagnose LPR without special instrumentation oropharyngeal findings may help the GP to diagnose and often manage LPR. In this review, we provide a practical algorithm for LPR management for GPs and other specialists that cannot perform fiberoptic examination. In this algorithm, physicians have to exclude some confounding conditions such as allergy or other causes of pharyngolaryngitis and “red flags”. They may prescribe an empirical treatment based on diet and behavioral changes with or without medication, depending on the symptom severity. Proton pump inhibitors and alginates remain a popular choice in order to protect the upper aerodigestive tract mucosa from acid, weakly acid and alkaline pharyngeal reflux events.
Troponin Elevation in Older Patients with Acute Pneumonia: Frequency and Prognostic Value
Authors: Putot Alain , Bouhey Emmanuel , Tetu Jennifer , Barben Jérémy , Timsit Eléonore , Putot Sophie , Ray Patrick , Manckoundia Patrick
Published: November 2020

Cardiovascular (CV) events are particularly frequent after acute pneumonia (AP) in the elderly. We aimed to assess whether cardiac troponin I, a specific biomarker of myocardial injury, independently predicts CV events and death after AP in older inpatients. Among 214 consecutive patients with AP aged ≥75 years admitted to a university hospital, 171 with a cardiac troponin I sample in the 72 h following diagnosis of AP were included, and 71 (42%) were found to have myocardial injury (troponin > 100 ng/L). Patients with and without myocardial injury were similar in terms of age, gender and comorbidities, but those with myocardial injury had more severe clinical presentation (median (interquartile range) Pneumonia Severity Index: 60 (40–95) vs. 45 (30–70), p = 0.003). Myocardial injury was strongly associated with in-hospital myocardial infarction (25% vs. 0%, p < 0.001), CV mortality (11 vs. 1%, p = 0.003) and all-cause mortality (34 vs. 13%, p = 0.002). After adjustment for confounders, myocardial injury remained a strong predictive factor of in-hospital mortality (odds ratio (95% confidence interval): 3.32 (1.42–7.73), p = 0.005) but not one-year mortality (1.61 (0.77–3.35), p = 0.2). Cardiac troponin I elevation, a specific biomarker of myocardial injury, was found in nearly half of an unselected cohort of older inpatients with AP and was associated with a threefold risk of in-hospital death.
Study on Toughness Improvement of a Rosin-Sourced Epoxy Matrix Composite for Green Aerospace Application
Authors: Hu Dongyuan , Zhang Xvfeng , Liu Xiaoling , Qin Zhen , Hu Li , Rudd Chris , Yi Xiaosu
Published: November 2020

A high temperature epoxy resin was formulated by using a rosin-sourced anhydride-type curing agent, i.e., maleopimaric acid (RAM), and a two-component epoxy consisting of an E51-type epoxy and a solid phenolic epoxy to form a bio-sourced green matrix resin. The glass transition temperature of the final resin was 238 °C Carbon fiber composite prepreg and was manufactured and laminated into composite specimens. Interleaving Toughening Technology (ITT) was applied to the laminates by using Polyamide interleaf veils. The interlaminar fracture toughness and compression after impact (CAI) strength were investigated and showed that the opening Mode I interlaminar fracture toughness GIC and the Mode II interlaminar fracture toughness GIIC of the specimens with interleaves were significantly improved from 227.51 J/m2 to 509.22 J/m2 and 1064.3 J/m2 to 1510.8 J/m2, respectively. Correspondingly, the drop-weight impact test shows that the interleaves reduced the impact damage area from 20.9% to 11.3% of the total area, and the CAI residual strength was increased from 144 MPa to 191 MPa. Meanwhile, mechanical tests showed that the in-plane properties of the interleaved laminates were slightly reduced due to carbon fiber volume fraction reduction. In conclusion, the high glass transition temperature, fracture toughness and CAI behaviour make the green resin matrix composite a potential candidate for aerospace applications.
Nordic Walking and Free Walking Improve the Quality of Life, Cognitive Function, and Depressive Symptoms in Individuals with Parkinson’s Disease: A Randomized Clinical Trial
Authors: Passos-Monteiro Elren , B. Schuch Felipe , T. Franzoni Leandro , R. Carvalho Alberito , A. Gomeñuka Natalia , Becker Marindia , Rieder Carlos R. M. , Andrade Alexandro , G. Martinez Flávia , S. Pagnussat Aline , A. Peyré-Tartaruga Leonardo
Published: November 2020

Nordic walking’s (NW) degree of effectiveness regarding health-related parameters in people with Parkinson’s Disease (PD) is a subject of debate. While NW seems to improve functionality, a clear non-motor benefit has not been demonstrated. The aim of this randomized controlled trial was to compare the effects of 9-week NW and free walking (FW) training programs on quality of life, cognitive function, and depressive symptoms in individuals with PD. Thirty-three people with PD, (Hoehn and Yahr 1–4) were randomized into two groups: NW (n = 16) and FW (n = 17). We analyzed quality of life, cognitive function, depressive symptoms, and motor symptoms. Significant improvements were found in the overall, physical, psychological, social participation, and intimacy domains of quality of life, as well as in cognitive function and depressive symptoms for both groups. Only the NW group showed improvement in the autonomy domain. Individuals with PD had a similar enhancement of non-motor symptoms after walking training, with or without poles. However, the NW group showed a more significant improvement in the autonomy domain, strengthening the applied and clinical potential of NW in people with PD. Future studies are needed to determine the efficacy of walking training without poles in subjects with PD.
Deep Learning in Selected Cancers’ Image Analysis—A Survey
Authors: Debelee Taye Girma , Kebede Samuel Rahimeto , Schwenker Friedhelm , Shewarega Zemene Matewos
Published: November 2020

Deep learning algorithms have become the first choice as an approach to medical image analysis, face recognition, and emotion recognition. In this survey, several deep-learning-based approaches applied to breast cancer, cervical cancer, brain tumor, colon and lung cancers are studied and reviewed. Deep learning has been applied in almost all of the imaging modalities used for cervical and breast cancers and MRIs for the brain tumor. The result of the review process indicated that deep learning methods have achieved state-of-the-art in tumor detection, segmentation, feature extraction and classification. As presented in this paper, the deep learning approaches were used in three different modes that include training from scratch, transfer learning through freezing some layers of the deep learning network and modifying the architecture to reduce the number of parameters existing in the network. Moreover, the application of deep learning to imaging devices for the detection of various cancer cases has been studied by researchers affiliated to academic and medical institutes in economically developed countries; while, the study has not had much attention in Africa despite the dramatic soar of cancer risks in the continent.
Incidence and Risk Factors of Chronic Pulmonary Aspergillosis Development during Long-Term Follow-Up after Lung Cancer Surgery
Authors: Shin Sun , Kim Bo-Guen , Kang Jiyeon , Um Sang-Won , Kim Hojoong , Kim Hong , Kim Jhingook , Shim Young , Choi Yong , Jeong Byeong-Ho
Published: November 2020

Lung resection surgery for non-small-cell lung cancer (NSCLC) is reportedly a risk factor for developing chronic pulmonary aspergillosis (CPA). However, limited data are available regarding the development of CPA during long-term follow-up after lung cancer surgery. This study aimed to investigate the cumulative incidence and clinical factors associated with CPA development after lung cancer surgery. We retrospectively analyzed 3423 patients with NSCLC who (1) underwent surgical resection and (2) did not have CPA at the time of surgery between January 2010 and December 2013. The diagnosis of CPA was based on clinical symptoms, serological or microbiological evidences, compatible radiological findings, and exclusion of alternative diagnoses. The cumulative incidence of CPA and overall survival (OS) were estimated using the Kaplan–Meier method, and a multivariable Cox proportional hazard analysis was performed to identify factors associated with CPA development. Patients were followed-up for a median of 5.83 years with a 72.3% 5-year OS rate. Fifty-six patients developed CPA at a median of 2.68 years after surgery, with cumulative incidences of 0.4%, 1.1%, 1.6%, and 3.5% at 1, 3, 5, and 10 years, respectively. Lower body mass index (BMI), smoking, underlying interstitial lung disease, thoracotomy, development of postoperative pulmonary complications 30 days after surgery, and treatment with both chemotherapy and radiotherapy were independently associated with CPA development. The cumulative incidence of CPA after surgery was 3.5% at 10 years and showed a steadily increasing trend during long-term follow-up. Therefore, increased awareness regarding CPA development is needed especially in patients with risk factors.
Evaluation of Cultivated Land Use Efficiency with Environmental Constraints in the Dongting Lake Eco-Economic Zone of Hunan Province, China
Authors: Chen Ying , Li Suran , Cheng Long
Published: November 2020

The rapid urban and industrial development in China has put pressure on the limited cultivated land resources. In ecologically fragile areas, such as the Dongting Lake Eco-economic Zone, land pollution and waste emissions from agricultural production cause irreversible damage to cultivated land. Thus, a method to assess the sustainability of cultivated land use efficiency (CLUE) is explored. Using the panel data of 25 districts in the province from 2007 to 2017, this study incorporates agricultural non-point source pollution and carbon emissions into undesirable outputs of cultivated land. The SBM(Slack-based Measure)-undesirable model was applied to measure the spatiotemporal characteristics of CLUE under environmental constraints. This study finds that CLUE with environmental constraints is significantly lower than CLUE without environmental constraints, and the degree of the impacts of the constraints differs among regions. Second, from 2007 to 2017, the average CLUE of the province showed a downward trend in each year; this is due to the side effects of redundant inputs and undesired outputs. Third, in 2017, the CLUE of the Dongting Lake Eco-economic Zone was high in the west and low in the east, and the redundant inputs of CLUE were livestock, fertilizer, and pesticide. The study concludes by recommending some policies.
Beyond Mere Text Frequency: Assessing Subtle Grammaticalization by Different Quantitative Measures. A Case Study on the Dutch Soort Construction
Authors: De Troij Robbert , Van de Velde Freek
Published: November 2020

Grammaticalization has proven to be an insightful approach to semantic-morphosyntactic change within and across languages. Many studies, however, rely on assessing the large, obvious differences before and after the change. When investigating burgeoning or ongoing grammaticalization processes, it is notably harder to objectively measure the degree of grammaticalization. One approach is to gauge changes in the well-known ‘parameters’ of Lehmann, Hopper, and Himmelmann, but this approach is often qualitatively oriented. Quantitative studies mainly rely either on token frequency of a construction, assuming that grammaticalization is accompanied by a frequency increase, or by tracing the development of two competing constructions, looking at the proportion of their respective token frequencies. In this article, we argue for a wider range of quantitative measures, beyond token frequency, as dependent variables. We will show that these measures can jointly point to subtle ongoing grammaticalization. As a case study, we will focus on Dutch binominals with soort ‘sort’, a core member of the much-discussed sort-kind-type (SKT) construction in the languages of Europe. Based on a large dataset of over 14,000 instances from the period between 1850 and 1999, we investigate quantitatively measurable changes in the construction’s surface behavior (i.e., the gradual loss of the relator van ‘of’ and increasing restrictions on premodification and pluralization, pointing to a process of ‘decategorialization’). In addition, we will also use Gries’s deviation of proportions (DP) to gauge the dispersion of soort, a valuable but under-used metric in quantitative studies of grammaticalization.
Chitosan-Based Thermo-Sensitive Hydrogel Loading Oyster Peptides for Hemostasis Application
Authors: Zhang Dongying , Hu Zhang , Zhang Lingyu , Lu Sitong , Liang Fengyan , Li Sidong
Published: November 2020

Uncontrolled massive hemorrhage is one of the principal causes of death in trauma emergencies. By using catechol-modified chitosan (CS-C) as the matrix material and β glycerol phosphate (β-GP) as a thermo-sensitive agent, chitosan-based thermo-sensitive hydrogel loading oyster peptides (CS-C/OP/β-GP) were prepared at physiological temperature. The hemostatic performance of CS-C/OP/β-GP hydrogel was tested in vivo and in vitro, and its biological safety was evaluated. The results showed that the in vitro coagulation time and blood coagulation index of CS-C/OP/β-GP hydrogel were better than those of a commercial gelatin sponge. Notably, compared with the gelatin sponge, CS-C/OP/β-GP hydrogel showed that the platelet adhesion and erythrocyte adsorption rates were 38.98% and 95.87% higher, respectively. Additionally, the hemostasis time in mouse liver injury was shortened by 19.5%, and the mass of blood loss in the mouse tail amputation model was reduced by 18.9%. The safety evaluation results demonstrated that CS-C/OP/β-GP had no cytotoxicity to L929 cells, and the hemolysis rates were less than 5% within 1 mg/mL, suggesting good biocompatibility. In conclusion, our results indicate that CS-C/OP/β-GP is expected to be a promising dressing in the field of medical hemostasis.