bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Ecological Diversity Analyses to Characterize the Availability of Healthy Food and Socio-Economic Food Deserts
Authors: Goyanes Annie , Hoch Jeffrey Matthew
Published: September 2021

“Food deserts” are usually defined as geographic areas without local access to fresh, healthy food. We used community ecology statistics in supermarkets to quantify the availability of healthy food and to potentially identify food deserts as areas without a diverse selection of food, rather than a binary as to whether fresh food is present or not. We test whether produce diversity is correlated with neighborhood income or demographics. Abundance and diversity of fresh produce was quantified in supermarkets in Broward County, Florida, USA. Neighborhood income level and racial/ethnic makeup were retrieved from the U.S. Census and American Community Survey. Although diversity varied, there were no communities that had consistently less available fresh food, although the percent of a neighborhood identifying as “white” was positively correlated with produce diversity. There may be fewer choices in neighborhoods with a higher proportion of minorities, but there were no consistent patterns of produce diversity in Broward County. This method demonstrates an easy, inexpensive way to characterize food deserts beyond simple distance, and results in precise enough information to identify gaps in the availability of healthy foods.
Efficacy of the FIBROWALK Multicomponent Program Moved to a Virtual Setting for Patients with Fibromyalgia during the COVID-19 Pandemic: A Proof-of-Concept RCT Performed Alongside the State of Alarm in Spain
Authors: Serrat Mayte , Coll-Omaña Mireia , Albajes Klara , Solé Sílvia , Almirall Miriam , Luciano Juan V. , Feliu-Soler Albert
Published: September 2021

FIBROWALK is a multicomponent program including pain neuroscience education, therapeutic exercise, cognitive behavioral therapy and mindfulness training that has recently been found to be effective in patients with fibromyalgia (FM). This RCT started before the COVID-19 pandemic and was moved to a virtual format (i.e., online videos) when the lockdown was declared in Spain. This study is aimed to evaluate the efficacy of a virtual FIBROWALK compared to Treatment-As-Usual (TAU) in patients with FM during the first state of alarm in Spain. A total of 151 patients with FM were randomized into two study arms: FIBROWALK plus TAU vs. TAU alone. The primary outcome was functional impairment. Secondary outcomes were kinesiophobia, anxiety and depressive symptomatology, and physical functioning. Differences between groups at post-treatment assessment were analyzed using Intention-To-Treat (ITT) and completer approaches. Baseline differences between clinical responders and non-responders were also explored. Statistically significant improvements with small-to-moderate effect sizes were observed in FIBROWALK+TAU vs. TAU regarding functional impairment and most secondary outcomes. In our study, the NNT was 5, which was, albeit modestly, indicative of an efficacious intervention. The results of this proof-of-concept RCT preliminarily support the efficacy of virtual FIBROWALK in patients with FM during the Spanish COVID-19 lockdown.
Prevalence of Mental Health Disorders among Elderly Diabetics and Associated Risk Factors in Indonesia
Authors: Azam Mahalul , Sulistiana Rina , Fibriana Arulita Ika , Savitri Soesmeyka , Aljunid Syed Mohamed
Published: September 2021

This cross-sectional study aimed to explore mental health disorders (MHD) prevalence among elderly diabetics in Indonesia. Data were extracted from the 2018 national basic health survey in Indonesia (abbreviated as RISKESDAS). The survey involved households randomly selected from 34 provinces, 416 districts, and 98 cities in Indonesia, with 1,017,290 respondents. The number of subjects selected in this study was 2818 elderly diabetic subjects. MHD was determined by self-reporting assessment. Secondary data acquired from RISKESDAS 2018 data involved age, sex, urban–rural residence status, marital status, educational level, employment status, obesity, hypertension, heart disease, stroke, family history of MHD, and DM duration. Binary logistic regression with a backward stepwise method was used to analyze the risk factors related to MHD. MHD prevalence among elderly diabetics in Indonesia was 19.3%. Factors associated with MHD among elderly diabetics were being female (prevalence odds ratio (POR) = 1.64; 95% CI: 1.126–2.394), married (POR = 0.05; 95% CI: 0.031–0.084), less education (POR = 3.37; 95% CI: 1.598–10.355), and stroke (POR = 1.61; 95% CI: 1.183–2.269). MHD prevalence among elderly diabetics in Indonesia was 19.3%, suggesting that screening for psychological problems and educating elderly diabetic patients is essential. Unmarried female elderly diabetics with less education and stroke were altogether more likely to experience MHD.
The Influence of Work–Family Conflict on Burnout during the COVID-19 Pandemic: The Effect of Teleworking Overload
Authors: Barriga Medina Holger Raúl , Campoverde Aguirre Ronald , Coello-Montecel David , Ochoa Pacheco Paola , Paredes-Aguirre Milton Ismael
Published: September 2021

If there is any field that has experienced changes as a result of the COVID-19 pandemic, it is work, primarily due to the implementation of teleworking and the effort made by workers and families to face new responsibilities. In this context, the study aims to analyze the impact of work–family conflict on burnout, considering work overload, in teleworkers during the COVID-19 pandemic. To evaluate the hypotheses, we used data collected during the last week of July 2020 using an online survey. Work–family conflict and burnout were measured using the Gutek et al. (1991) and Shirom (1989) scales. We tested the hypotheses using a structural equation model (SEM). The results indicated, between other findings, that there was a positive relationship between work–family conflict and family–work conflict and all the dimensions of burnout. However, there was no effect of teleworking overload in the work–family conflict and burnout relationship. This article is innovative because it highlights the importance of the economic and regulatory conditions that have surrounded the modality of teleworking during the pandemic, and their influence on wellbeing and psychosocial risks in workers.
Pain Rehabilitation’s Effect on People in Chronic Pain: A Prospective Cohort Study
Authors: Skúladóttir Hafdís , Björnsdottir Amalia , Holden Janean E. , Gunnarsdóttir Thóra Jenný , Halldorsdottir Sigridur , Sveinsdottir Herdis
Published: September 2021

Multidisciplinary long-term pain rehabilitation programs with a team of healthcare professionals are an integrated approach to treat patients with chronic non-malignant pain. In this longitudinal prospective cohort study, we investigated the long-term effects of multidisciplinary pain rehabilitation on the self-reported causes of pain, pain self-management strategies, sleep, pain severity, and pain’s interference with life, pre- and post-treatment. Eighty-one patients, aged 20–69 years, with chronic pain responded. The two most frequently reported perceived causes of pain were fibromyalgia and accidents. The difference in average self-reported pain severity decreased significantly at one-year follow-up (p < 0.001), as did pain’s interference with general activities, mood, walking ability, sleep, and enjoyment of life. At one-year follow-up, participants (21%) rated their health as good/very good and were more likely to state that it was better than a year before (20%). No change was found in the use of pain self-management strategies such as physical training at one-year follow-up. The intervention was effective for the participants, as reflected in the decreased pain severity and pain interference with life.
Application of Solid Phase Extraction and High-Performance Liquid Chromatography with Fluorescence Detection to Analyze Bisphenol A Bis (2,3-Dihydroxypropyl) Ether (BADGE 2H2O), Bisphenol F (BPF), and Bisphenol E (BPE) in Human Urine Samples
Authors: Tuzimski Tomasz , Szubartowski Szymon
Published: September 2021

In this study, we propose a simple, cost-effective, and sensitive high-performance liquid chromatography method with fluorescence detection (HPLC-FLD) for the simultaneous determination of the three bisphenols (BPs): bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE 2H2O), bisphenol F (BPF), and bisphenol E (BPE) in human urine samples. The dispersive solid phase extraction (d-SPE) coupled with solid phase extraction (SPE) procedure performed well for the analytes with recoveries in the range of 74.3–86.5% and relative standard deviations (RSD%) less than 10%. The limits of quantification (LOQs) for all investigated analytes were in the range of 11.42–22.35 ng mL−1. The method was validated at three concentration levels (1 × LOQ, 1.5 × LOQ, and 3 LOQ). During the bisphenols HPLC-FLD analysis, from 6 min a reinforcement (10 or 12) was used, therefore analytes might be identified in the small volume human urine samples. The results demonstrated clearly that the approach developed provides reliable, simple, and rapid quantification and identification of three bisphenols in a urine matrix and could be used for monitoring these analytes.
Geochemical Control of PAHs by Inflowing River Water to West Nanao Bay, Japan, and Its Influences on Ecological Risk: Small-Scale Changes Observed under Near-Background Conditions at an Enclosed Bay
Authors: Mundo Rodrigo , Matsunaka Tetsuya , Iwai Hisanori , Ochiai Shinya , Nagao Seiya
Published: September 2021

Polycyclic aromatic hydrocarbons (PAHs), even at low concentrations, have been shown to trigger changes in life cycles and provoke abnormal behaviors in numerous marine organisms. From May 2019 to September 2020, particulate and dissolved PAH concentrations were analyzed on the surface water of West Nanao Bay, Japan, to determinate their levels, emission sources, environmental pathways, and ecological risks at this remote but semi-enclosed bay. The 14 targeted PAHs were analyzed by HPLC-fluorescence detector. Mean total PAH concentrations were lower than 20.0 ng L−1 for most samples. Based on fluoranthene (Flu) to pyrene (Pyr) ([Flu]/[Flu + Pyr]) and benzo[a]anthracene (BaA) to chrysene (Chr) ([BaA]/[BaA + Chr]) isomeric ratios and a varimax rotated PCA, it was established that biomass combustion was the principal source in the particulate phase and that liquid fossil fuel combustion was the principal source in the dissolved phase. From salinity and turbidity distribution, riverine discharges were determined to be the major and continuous transportation pathway of particulate PAHs. It was observed that rain events had a role in the transport of dissolved PAHs. The risk quotients (RQ∑14 PAHs (NCs): 0–84.53) indicated that PAHs represented a very low to low acute environmental risk. The results of this study will contribute to filling the paradigm gap of ecotoxicological studies in remote areas, working as a booster for future in-lab studies of non-lethal implications of endocrine disruptors such as PAHs.
Blood Lead Levels and Cardiovascular Disease Risk: Results from the Korean National Health and Nutrition Examination Survey
Authors: Park Yoonjin , Han Jungjin
Published: September 2021

(1) Objective: Lead, a heavy metal that exists commonly in air, soil and crops may cause chronic disease in the cardiovascular system. The purpose of this study is to investigate how blood lead levels affect cardiovascular disease in adults. (2) Study Design and Participants: It is a cross-sectional, descriptive study using data from the Korean National Health and Nutrition Examination Survey (KNHANES). Data from a total of 1929 participants, derived from the KNHANES, conducted by the Korea Centers for Disease Control and Prevention, in 2017, were analyzed using SPSS version 25.0. (3) Measurement: The cardiovascular disease risk was calculated using the Framingham risk score. There was a strong positive correlation between blood lead levels and the Framingham risk score. Furthermore, of the FRS sub-criteria, systolic blood pressure, HDL cholesterol level and total cholesterol level all also showed a significant correlation. (4) Results: We analyzed the correlation between PbB levels and the FRS sub-criteria, including systolic blood pressure, HDL cholesterol level, total cholesterol level and the FRS total. We found a significant positive correlation between PbB levels and systolic blood pressure, FRS total and total cholesterol level (p < 0.05), as well as a significant negative correlation with HDL cholesterol level (p < 0.05). (5) Conclusion: Based on the perception that there is no lower toxicological threshold for blood lead, it is necessary to restrict lead in product manufacturing for the purpose of public health. In addition, it is necessary to be aware of the dangers of exposure to even small amounts of lead in daily life.
Green Line Hospital-Territory Study: A Single-Blind Randomized Clinical Trial for Evaluation of Technological Challenges of Continuous Wireless Monitoring in Internal Medicine, Preliminary Results
Authors: Pietrantonio Filomena , Vinci Antonio , Rosiello Francesco , Alessi Elena , Pascucci Matteo , Rainone Marianna , Delli Castelli Michela , Ciamei Angela , Montagnese Fabrizio , D’Amico Roberto , Valerio Antonella , Manfellotto Dario
Published: September 2021

Background: Wireless vital parameter continuous monitoring (WVPCM) after discharge is compared to regular monitoring to provide data on the clinical-economic impact of complex patients (CPs) discharged from Internal Medicine Units of Ospedale dei Castelli, Lazio. Primary outcome: Major complications (MC) reduction. Secondary outcomes: Patients who reached discharge criteria within the 7th day from admission; difference in MC incidence at the conclusion of the standard telemonitoring/clinical monitoring phase, 5 and 30 days after discharge; and conditions predisposing to MC occurrence. Methods: Open label randomized controlled trial with wearable wireless system that creates alerts on portable devices. Continuous glycemic monitoring is performed for patients with diabetes mellitus. Results: There were 110 patients enrolled (mean age: 76.2 years). Comorbidity: Cumulative Illness Rating Scale CIRS-CI (comorbidities index): 3.93, CIRS SI (severity index): 1.93. About 19% scored a BRASS (Blaylock Risk Assessment Screening Score) ≥20 indicating need for discharge planning requiring step-down care. Globally, 48% of patients in the control group had major complications (27 out of 56 patients), in contrast to 22% in the intervention group (12 out of 54 patients). Conclusions: Since WVPCM detects early complications during the post-discharge CPs monitoring, it increases safety and reduces inappropriate access to the Emergency Room, preventing avoidable re-hospitalizations.
Sequestration of RBM10 in Nuclear Bodies: Targeting Sequences and Biological Significance
Authors: Wang Ling-Yu , Xiao Sheng-Jun , Kunimoto Hiroyuki , Tokunaga Kazuaki , Kojima Hirotada , Kimura Masatsugu , Yamamoto Takahiro , Yamamoto Naoki , Zhao Hong , Nishio Koji , Tani Tokio , Nakajima Koichi , Sunami Kishiko , Inoue Akira
Published: September 2021

RBM10 is an RNA-binding protein that regulates alternative splicing (AS). It localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs) in the nucleus. We investigated the biological significance of this localization in relation to its molecular function. Our analyses, employing deletion mutants, revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs act synergistically to localize RBM10 to S1-1 NBs. The C2H2 ZnF not only acts as an NBTS, but is also essential for AS regulation by RBM10. Moreover, RBM10 does not participate in S1-1 NB formation, and without alterations of RBM10 protein levels, its NB-localization changes, increasing as cellular transcriptional activity declines, and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in NBs via its NBTSs when cellular transcription decreases. We propose that the C2H2 ZnF exerts its NB-targeting activity when RBM10 is unbound by pre-mRNAs, and that NB-localization of RBM10 is a mechanism to control its AS activity in the nucleus.
N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition
Authors: Pagano Cristina , Navarra Giovanna , Pastorino Olga , Avilia Giorgio , Coppola Laura , Della Monica Rosa , Chiariotti Lorenzo , Florio Tullio , Corsaro Alessandro , Torelli Giovanni , Caiazzo Pasquale , Gazzerro Patrizia , Bifulco Maurizio , Laezza Chiara
Published: September 2021

Background: Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells. Thus far, no effective drugs have been developed to target VM. Glioblastoma (GBM) is the most malignant form of brain cancer and is a highly vascularized tumor. Vasculogenic mimicry represents a means whereby GBM can escape anti-angiogenic therapies. Methods: Here, using an in vitro tube formation assay on Matrigel, we evaluated the ability of N6-isopentenyladenosine (iPA) to interfere with vasculogenic mimicry (VM). RhoA activity was assessed using a pull-down assay, while the modulation of the adherens junctions proteins was analyzed by Western blot analysis. Results: We found that iPA at sublethal doses inhibited the formation of capillary-like structures suppressing cell migration and invasion of U87MG, U343MG, and U251MG cells, of patient-derived human GBM cells and GBM stem cells. iPA reduces the vascular endothelial cadherin (VE-cadherin) expression levels in a dose-dependent manner, impairs the vasculogenic mimicry network by modulation of the Src/p120-catenin pathway and inhibition of RhoA-GTPase activity. Conclusions: Taken together, our results revealed iPA as a promising novel anti-VM drug in GBM clinical therapeutics.
Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts
Authors: Bayer Andreas , Wijaya Bernard , Rademacher Franziska , Möbus Lena , Preuß Mark , Singh Michael , Tohidnezhad Mersedeh , Kubo Yusuke , Rodewald Meno , Behrendt Peter , Weitkamp Jan-Tobias , Gläser Regine , Harder Jürgen
Published: September 2021

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products.
Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids
Authors: Torrens-Mas Margalida , Perelló-Reus Catalina , Navas-Enamorado Cayetano , Ibargüen-González Lesly , Sanchez-Polo Andres , Segura-Sampedro Juan Jose , Masmiquel Luis , Barcelo Carles , Gonzalez-Freire Marta
Published: September 2021

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. An organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.
Sustained Activation of TNFα-Induced DNA Damage Response in Newly Differentiated Adipocytes
Authors: Valverde Mahara , Sánchez-Brito Aarón
Published: September 2021

The response to DNA damage is the mechanism that allows the interaction between stress signals, inflammatory secretions, DNA repair, and maintenance of cell and tissue homeostasis. Adipocyte dysfunction is the cellular trigger for various disease states such as insulin resistance, diabetes, and obesity, among many others. Previously, our group demonstrated that adipogenesis per se, from mesenchymal/stromal stem cells derived from human adipose tissue (hASCs), involves an accumulation of DNA damage and a gradual loss of the repair capacity of oxidative DNA damage. Therefore, our objective was to identify whether healthy adipocytes differentiated for the first time from hASCs, when receiving inflammatory signals induced with TNFα, were able to persistently activate the DNA Damage Response and thus trigger adipocyte dysfunction. We found that TNFα at similar levels circulating in obese humans induce a sustained response to DNA damage response as part of the Senescence-Associated Secretory Phenotype. This mechanism shows the impact of inflammatory environment early affect adipocyte function, independently of aging.
Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury
Authors: Kyyriäinen Jenni , Kajevu Natallie , Bañuelos Ivette , Lara Leonardo , Lipponen Anssi , Balosso Silvia , Hämäläinen Elina , Das Gupta Shalini , Puhakka Noora , Natunen Teemu , Ravizza Teresa , Vezzani Annamaria , Hiltunen Mikko , Pitkänen Asla
Published: September 2021

We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% (p < 0.001) and neuroinflammation to –29% (p < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (p < 0.001). The effect of NAC was negligible, however, compared with SFN. In vivo, antioxidant duotherapy slightly improved performance in the beam walking test. Interestingly, duotherapy treatment decreased the plasma interleukin-6 and TNF levels in sham-operated controls (p < 0.05). After TBI, no treatment effect on HMGB1 or plasma cytokine levels was detected. Also, no treatment effects on the composite neuroscore or cortical lesion area were detected. The robust favorable effect of duotherapy on neuroprotection, neuroinflammation, and oxidative stress in neuron-BV2 microglial co-cultures translated to modest favorable in vivo effects in a severe TBI model.
IL-33/ST2 Axis Plays a Protective Effect in Streptococcus pyogenes Infection through Strengthening of the Innate Immunity
Authors: Kuo Chih-Feng , Chen Wei-Yu , Yu Hai-Han , Tsai Yu-Hsuan , Chang Ya-Chu , Chang Chih-Peng , Tsao Nina
Published: September 2021

Group A Streptococcus (GAS) causes invasive human diseases with the cytokine storm. Interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis is known to drive TH2 response, while its effect on GAS infection is unclear. We used an air pouch model to examine the effect of the IL-33/ST2 axis on GAS-induced necrotizing fasciitis. GAS infection induced IL-33 expression in wild-type (WT) C57BL/6 mice, whereas the IL-33- and ST2-knockout mice had higher mortality rates, more severe skin lesions and higher bacterial loads in the air pouches than those of WT mice after infection. Surveys of infiltrating cells in the air pouch of GAS-infected mice at the early stage found that the number and cell viability of infiltrating cells in both gene knockout mice were lower than those of WT mice. The predominant effector cells in GAS-infected air pouches were neutrophils. Absence of the IL-33/ST2 axis enhanced the expression of inflammatory cytokines, but not TH1 or TH2 cytokines, in the air pouch after infection. Using in vitro assays, we found that the IL-33/ST2 axis not only enhanced neutrophil migration but also strengthened the bactericidal activity of both sera and neutrophils. These results suggest that the IL-33/ST2 axis provided the protective effect on GAS infection through enhancing the innate immunity.
Extracellular Vesicles and Cancer Stem Cells in Tumor Progression: New Therapeutic Perspectives
Authors: Scioli Maria Giovanna , Terriaca Sonia , Fiorelli Elena , Storti Gabriele , Fabbri Giulia , Cervelli Valerio , Orlandi Augusto
Published: September 2021

Tumor burden is a complex microenvironment where different cell populations coexist and have intense cross-talk. Among them, a heterogeneous population of tumor cells with staminal features are grouped under the definition of cancer stem cells (CSCs). CSCs are also considered responsible for tumor progression, drug resistance, and disease relapse. Furthermore, CSCs secrete a wide variety of extracellular vesicles (EVs) with different cargos, including proteins, lipids, ssDNA, dsDNA, mRNA, siRNA, or miRNA. EVs are internalized by other cells, orienting the microenvironment toward a protumorigenic and prometastatic one. Given their importance in tumor growth and metastasis, EVs could be exploited as a new therapeutic target. The inhibition of biogenesis, release, or uptake of EVs could represent an efficacious strategy to impair the cross-talk between CSCs and other cells present in the tumor microenvironment. Moreover, natural or synthetic EVs could represent suitable carriers for drugs or bioactive molecules to target specific cell populations, including CSCs. This review will discuss the role of CSCs and EVs in tumor growth, progression, and metastasis and how they affect drug resistance and disease relapse. Furthermore, we will analyze the potential role of EVs as a target or vehicle of new therapies.
miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis
Authors: Hsu Chih-Hsin , Liu I-Fan , Kuo Hsuan-Fu , Li Chia-Yang , Lian Wei-Shiung , Chang Chia-Yuan , Chen Yung-Hsiang , Liu Wei-Lun , Lu Chi-Yu , Liu Yu-Ru , Lin Tzu-Chieh , Lee Tsung-Ying , Huang Chi-Yuan , Hsieh Chong-Chao , Liu Po-Len
Published: September 2021

Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung progression and liver fibrosis by regulating ECM protein expression; however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.
Roles of Two Small Leucine-Rich Proteoglycans Decorin and Biglycan in Pregnancy and Pregnancy-Associated Diseases
Authors: Halari Chidambra D. , Zheng Michael , Lala Peeyush K.
Published: September 2021

Two small leucine-rich proteoglycans (SLRP), decorin and biglycan, play important roles in structural–functional integrity of the placenta and fetal membranes, and their alterations can result in several pregnancy-associated diseases. In this review, we briefly discuss normal placental structure and functions, define and classify SLRPs, and then focus on two SLRPs, decorin (DCN) and biglycan (BGN). We discuss the consequences of deletions/mutations of DCN and BGN. We then summarize DCN and BGN expression in the pregnant uterus, myometrium, decidua, placenta, and fetal membranes. Actions of these SLRPs as ligands are then discussed in the context of multiple binding partners in the extracellular matrix and cell surface (receptors), as well as their alterations in pathological pregnancies, such as preeclampsia, fetal growth restriction, and preterm premature rupture of membranes. Lastly, we raise some unanswered questions as food for thought.
Rhamnolipids as Effective Green Agents in the Destabilisation of Dolomite Suspension
Authors: Legawiec Krzysztof Jan , Kruszelnicki Mateusz , Bastrzyk Anna , Polowczyk Izabela
Published: September 2021

In this paper, we describe an application of mono- and dirhamnolipid homologue mixtures of a biosurfactant as a green agent for destabilisation of a dolomite suspension. Properties of the biosurfactant solution were characterised using surface tension and aggregate measurements to prove aggregation of rhamnolipids at concentrations much lower than the critical micelle concentration. Based on this information, the adsorption process of biosurfactant molecules on the surface of the carbonate mineral dolomite was investigated, and the adsorption mechanism was proposed. The stability of the dolomite suspension after rhamnolipid adsorption was investigated by turbidimetry. The critical concentration of rhamnolipid at which destabilisation of the suspension occurred most effectively was found to be 50 mg·dm−3. By analysing backscattering profiles, solid-phase migration velocities were calculated. With different amounts of biomolecules, this parameter can be modified from 6.66 to 20.29 mm·h−1. Our study indicates that the dolomite suspension is destabilised by hydrophobic coagulation, which was proved by examining the wetting angle of the mineral surface using the captive bubble technique. The relatively low amount of biosurfactant used to destabilise the system indicates the potential application of this technology for water treatment or modification of the hydrophobicity of mineral surfaces in mineral engineering.
Esterase Activity of Serum Albumin Studied by 1H NMR Spectroscopy and Molecular Modelling
Authors: Belinskaia Daria A. , Voronina Polina A. , Vovk Mikhail A. , Shmurak Vladimir I. , Batalova Anastasia A. , Jenkins Richard O. , Goncharov Nikolay V.
Published: September 2021

Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (1H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin.
A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity
Authors: Howe Orla , White Lisa , Cullen Daniel , O’Brien Grainne , Shields Laura , Bryant Jane , Noone Emma , Bradshaw Shirley , Finn Marie , Dunne Mary , Shannon Aoife M. , Armstrong John , McClean Brendan , Meade Aidan , Badie Christophe , Lyng Fiona M.
Published: September 2021

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.
Leptin Reduces Plin5 m6A Methylation through FTO to Regulate Lipolysis in Piglets
Authors: Wei Dongqin , Sun Qian , Li Yizhou , Li Chaowei , Li Xinjian , Sun Chao
Published: September 2021

Perilipin5 (Plin5) is a scaffold protein that plays an important role in lipid droplets (LD) formation, but the regulatory effect of leptin on it is unclear. Our study aimed to explore the underlying mechanisms by which leptin reduces the N6-methyladenosine (m6A) methylation of Plin5 through fat mass and obesity associated genes (FTO) and regulates the lipolysis. To this end, 24 Landrace male piglets (7.73 ± 0.38 kg) were randomly sorted into two groups, either a control group (Control, n = 12) or a 1 mg/kg leptin recombinant protein treatment group (Leptin, n = 12). After 4 weeks of treatment, the results showed that leptin treatment group had lower body weight, body fat percentage and blood lipid levels, but the levels of Plin5 mRNA and protein increased significantly in adipose tissue (p < 0.05). Leptin promotes the up-regulation of FTO expression level in vitro, which in turn leads to the decrease of Plin5 M6A methylation (p < 0.05). In in vitro porcine adipocytes, overexpression of FTO aggravated the decrease of M6A methylation and increased the expression of Plin5 protein, while the interference fragment of FTO reversed the decrease of m6A methylation (p < 0.05). Finally, the overexpression in vitro of Plin5 significantly reduces the size of LD, promotes the metabolism of triglycerides and the operation of the mitochondrial respiratory chain, and increases thermogenesis. This study clarified that leptin can regulate Plin5 M6A methylation by promoting FTO to affect the lipid metabolism and energy consumption, providing a theoretical basis for treating diseases related to obesity.
Selected Biomarkers of Tick-Borne Encephalitis: A Review
Authors: Gudowska-Sawczuk Monika , Mroczko Barbara
Published: September 2021

Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system—most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.
The FMN “140s Loop” of Cytochrome P450 Reductase Controls Electron Transfer to Cytochrome P450
Authors: Rwere Freeborn , Im Sangchoul , Waskell Lucy
Published: September 2021

Cytochrome P450 reductase (CYPOR) provides electrons to all human microsomal cytochrome P450s (cyt P450s). The length and sequence of the “140s” FMN binding loop of CYPOR has been shown to be a key determinant of its redox potential and activity with cyt P450s. Shortening the “140s loop” by deleting glycine-141(ΔGly141) and by engineering a second mutant that mimics flavo-cytochrome P450 BM3 (ΔGly141/Glu142Asn) resulted in mutants that formed an unstable anionic semiquinone. In an attempt to understand the molecular basis of the inability of these mutants to support activity with cyt P450, we expressed, purified, and determined their ability to reduce ferric P450. Our results showed that the ΔGly141 mutant with a very mobile loop only reduced ~7% of cyt P450 with a rate similar to that of the wild type. On the other hand, the more stable loop in the ΔGly141/Glu142Asn mutant allowed for ~55% of the cyt P450 to be reduced ~60% faster than the wild type. Our results reveal that the poor activity of the ΔGly141 mutant is primarily accounted for by its markedly diminished ability to reduce ferric cyt P450. In contrast, the poor activity of the ΔGly141/Glu142Asn mutant is presumably a consequence of the altered structure and mobility of the “140s loop”.
Use of Echocardiography and Heart Failure In-Hospital Mortality from Registry Data in Japan
Authors: Kusunose Kenya , Okushi Yuichiro , Okayama Yoshihiro , Zheng Robert , Nakai Michikazu , Sumita Yoko , Ise Takayuki , Yamaguchi Koji , Yagi Shusuke , Fukuda Daiju , Yamada Hirotsugu , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: September 2021

Background: Echocardiography requires a high degree of skill on the part of the examiner, and the skill may be more improved in larger volume centers. This study investigated trends and outcomes associated with the use and volume of echocardiographic exams from a real-world registry database of heart failure (HF) hospitalizations. Methods: This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). A first analysis was performed to assess the trend of echocardiographic examinations between 2012 and 2016. A secondary analysis was performed to assess whether echocardiographic use was associated with in-hospital mortality in 2015. Results: During this period, the use of echocardiography grew at an average annual rate of 6%. Patients with echocardiography had declining rates of hospital mortality, and these trends were associated with high hospitalization costs. In the 2015 sample, a total of 52,832 echocardiograms were examined, corresponding to 65.6% of all HF hospital admissions for that year. We found that the use and volume of echocardiography exams were associated with significantly lower odds of all-cause hospital mortality in heart failure (adjusted odds ratio (OR): 0.48 for use of echocardiography and 0.78 for the third tertile; both p < 0.001). Conclusions: The use of echocardiography was associated with decreased odds of hospital mortality in HF. The volumes of echocardiographic examinations were also associated with hospital mortality.
Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment
Authors: Knoppova Barbora , Reily Colin , King R. Glenn , Julian Bruce A. , Novak Jan , Green Todd J.
Published: September 2021

IgA nephropathy, initially described in 1968 as a kidney disease with glomerular “intercapillary deposits of IgA-IgG”, has no disease-specific treatment and is a common cause of kidney failure. Clinical observations and laboratory analyses suggest that IgA nephropathy is an autoimmune disease wherein the kidneys are damaged as innocent bystanders due to deposition of IgA1-IgG immune complexes from the circulation. A multi-hit hypothesis for the pathogenesis of IgA nephropathy describes four sequential steps in disease development. Specifically, patients with IgA nephropathy have elevated circulating levels of IgA1 with some O-glycans deficient in galactose (galactose-deficient IgA1) and these IgA1 glycoforms are recognized as autoantigens by unique IgG autoantibodies, resulting in formation of circulating immune complexes, some of which deposit in glomeruli and activate mesangial cells to induce kidney injury. This proposed mechanism is supported by observations that (i) glomerular immunodeposits in patients with IgA nephropathy are enriched for galactose-deficient IgA1 glycoforms and the corresponding IgG autoantibodies; (ii) circulatory levels of galactose-deficient IgA1 and IgG autoantibodies predict disease progression; and (iii) pathogenic potential of galactose-deficient IgA1 and IgG autoantibodies was demonstrated in vivo. Thus, a better understanding of the structure–function of these immunoglobulins as autoantibodies and autoantigens will enable development of disease-specific treatments.
Postoperative Pain following Root Canal Filling with Bioceramic vs. Traditional Filling Techniques: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Mekhdieva Elina , Del Fabbro Massimo , Alovisi Mario , Comba Allegra , Scotti Nicola , Tumedei Margherita , Carossa Massimo , Berutti Elio , Pasqualini Damiano
Published: September 2021

This meta-analysis aimed to evaluate postoperative pain (POP) following root canal filling (RCF) with gutta-percha/bioceramic sealer (BCS) vs. gutta-percha/traditional sealer (TS) techniques. Electronic databases were searched for randomized trials. Subgroup analyses were performed for analgesic intake, flare-ups, postoperative time (24/48 h), pulp status, and retreatment. The search yielded 682 records, and nine studies were selected. BCS was associated with significantly lower POP vs. TS at 24 h (P = 0.04) and 48 h (P = 0.0005). In addition, non-significant trends favoring BCS for analgesic intake at 24 h (P = 0.14), flare-ups (P = 0.24) and obturation techniques at 24 h (P = 0.41) and 48 h (P = 0.33), non-significant trends for lower POP with TS vs. BCS 24 h and 48 h in vital teeth (P = 0.50, P = 0.18, respectively), and for lower POP with BCS vs. TS in non-vital teeth at 24 h and 48 h (P = 0.16, P = 0.84, respectively). POP was numerically lower with TS vs. BCS at 24 h (P = 0.65) and 48 h after retreatment (P = 0.59). Moreover, POP did not vary between fillers when the treatment was over single (P = 0.28) or multiple visits (P = 0.50). BCS was associated with significantly lower short-term POP, and with a trend for lower analgesic intake and flare-up incidence, as compared to TS.
Therapeutic and Reconstructive Management Options in Scleroderma (Morphea) en Coup de Sabre in Children and Adults. A Systematic Literature Review
Authors: Ulc Ewelina , Rudnicka Lidia , Waśkiel-Burnat Anna , Warszawik-Hendzel Olga , Niemczyk Anna , Olszewska Małgorzata
Published: September 2021

Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of evidence, primarily case reports and case series-supported by expert opinions. The aim of this article was to systematically analyze current data related to the treatment of localized scleroderma en coup de sabre. The databases Scopus, PubMed, and EBSCO were searched for all reports discussing the treatment of localized scleroderma en coup de sabre. The keywords en coup de sabre, “facial linear scleroderma”, and “morphea linearis”, combined with “treatment” or “therapy” were used as search terms. A total of 34 articles analyzed treatment outcomes for patients with localized scleroderma en coup de sabre including 4 retrospective cohort studies, 2 prospective cohort studies, 4 case series, and 24 case reports, representing a total of 69 patients (38 children and 31 adults). Methotrexate was the most commonly investigated treatment (26 patients) with a highest response rate (26/26, 100%). Other treatments included systemic glucocorticosteroids (nine patients), followed by UVA1 (four patients), mycophenolate mofetil (two patients), hydroxychloroquine (five patients), abatacept (two patients), tocilizumab (three patients), cyclosporine (one patient), interferon gamma (one patient), PUVA therapy (two patients), NB-UVB therapy (one patient), and pulsed dye laser (one patient). Reconstructive and surgery treatment was successfully used for lesions with settled disease activity to improve the cosmetic aspect of the lesions. Conclusion: methotrexate is the most often-studied treatment and reported good clinical outcomes in children and adults with localized scleroderma en coup de sabre.