bluuebunny/crossref_metadata_2025 huggingface dataset:
What Drives the Food Safety Certification: A Qualitative Comparative Analysis of Food Companies in China
Authors: Lin Quan , Zhang Nana , Guan Wanchao
Published: June 2021

Food safety is related to health and quality of life. Therefore, the social responsibility of the food industry to ensure food safety has received increasing attention. Influencing factors and mechanisms of participation in food safety certification are important issues in this field. Existing studies on factors affecting food safety certification mainly focus on the impact of a single or few factors. In this study, listed Chinese food companies were selected, and the fuzzy set qualitative comparative analysis method was utilized to explore the matching mode of various factors to encourage companies to obtain food safety certification. The following results were obtained. (1) State-owned companies tend to achieve food safety certification. (2) Companies with high media attention are inclined to achieve food safety certification. (3) In state-owned companies, when the company size is small, a higher degree of food safety concern in the mission statement can encourage the company to achieve food safety certification, and when the company size is large, higher media attention can encourage the company to achieve food safety certification. (4) In non-state-owned companies, when food safety concerns are highlighted in the mission statement and media attention is relatively high, the company will gain food safety certification. This study provides new perspectives on food safety-related research and suggestions for government and the public sector to supervise food safety issues in enterprises.
Anemia and Nutritional Status of Syrian Refugee Mothers and Their Children under Five Years in Greater Beirut, Lebanon
Authors: Abou-Rizk Joana , Jeremias Theresa , Nasreddine Lara , Jomaa Lamis , Hwalla Nahla , Tamim Hani , Frank Jan , Scherbaum Veronika
Published: June 2021

The objective was to assess the prevalence of anemia and nutritional status of mothers and children under five years among Syrian refugees in Lebanon and to identify nutritional deficiencies among pregnant, lactating, and non-pregnant non-lactating (NPNLM) mothers. A cross-sectional study was conducted among Syrian refugee mothers with children under five years in Greater Beirut, Lebanon (n = 433). Data on socio-economic status, maternal health, lifestyle characteristics, dietary intake, anthropometric measurements, and hemoglobin concentrations were collected. The prevalence of anemia was 21.7% among mothers and 30.5% among children. NPNLM with overweight/obesity and an at-risk waist circumference (WC) had 14.7-times and 10.9-times higher odds of anemia than mothers with normal WC and weight. Children of anemic mothers had 2.7-times and 4.4-times higher odds of total and mild anemia than those of non-anemic. Higher odds of mild anemia were found among children of lactating mothers than of NPNLM. A high percent energy intake of total fat and sugar was found among all mothers. Nutritional inadequacy was identified in higher proportions of lactating and pregnant mothers than NPNLM. Our findings highlighted the co-existence of overnutrition and anemia among Syrian refugee mothers and undernutrition among children from the same household. Culture-specific interventions are needed to support maternal nutrition, to ensure the health and wellbeing of their offspring.
Nature-Based Rehabilitation for Patients with Long-Standing Stress-Related Mental Disorders: A Qualitative Evidence Synthesis of Patients’ Experiences
Authors: Bergenheim Anna , Ahlborg Gunnar , Bernhardsson Susanne
Published: June 2021

Stress-related mental disorders contribute to work disabilities globally and are a common cause for sick leave. Nature-based rehabilitation (NBR) is a multi-disciplinary approach offered to this patient group on a limited scale. Qualitative studies provide insight into patients’ experiences of NBR, and there is a need to synthesize and assess the certainty of evidence for patient-experienced benefits. The aim was to identify, appraise, and synthesize studies reporting experiences and perceived benefits of participation in multidisciplinary, group-based NBR of adult patients with long-standing stress-related mental disorders. PubMed, Embase, CINAHL, AMED, APA PsycInfo, and the Cochrane Library were searched from inception to December 2020. Reference lists of relevant publications were searched. After title and abstract screening, full-text articles were retrieved and assessed for inclusion. The methodological quality of the included studies was assessed, and certainty of evidence was appraised according to CERQual. The search yielded 362 unique records; 19 full-text publications were assessed for eligibility, and 5 studies were included in the synthesis. The studies were considered relevant regarding context, population, and intervention, and quality was generally assessed as moderate to high. Extracted texts were inductively coded and organized into 16 descriptive themes and 4 broad, analytical themes: Instilling calm and joy; Needs being met; Gaining new insights; and Personal growth. Experiences and perceived benefits of participating in NBR and spending time in a nature environment were described as positive for recovery. Nine of the descriptive themes were based on explicit results from at least four of the five studies. Confidence in the evidence of the qualitative findings ranged from moderate to low. Moderate-to-low certainty evidence from the included studies suggests that patients with long-standing stress-related mental disorders experience positive health effects from participating in NBR.
Mesocosm Experiments to Quantify Predation of Mosquito Larvae by Aquatic Predators to Determine Potential of Ecological Control of Malaria Vectors in Ethiopia
Authors: Olkeba Beekam Kebede , Goethals Peter L. M. , Boets Pieter , Duchateau Luc , Degefa Teshome , Eba Kasahun , Yewhalaw Delenasaw , Mereta Seid Tiku
Published: June 2021

Malaria parasites are transmitted to humans by infectious female Anopheles mosquitoes. Chemical-insecticide-based mosquito control has been successful in reducing the burden of malaria. However, the emergence of insecticide resistance in malaria vectors and concerns about the effect of the chemicals on the environment, human health, and non-target organisms present a need for new or alternative vector control intervention tools. Biocontrol methods using aquatic invertebrate predators have emerged as a potential alternative and additional tool to control mosquito populations. Ecological control specifically makes use of species insights for improving the physical habitat conditions of competitors and predators of vectors. A first step towards this is to gain knowledge on the predation potential of several typically present macroinvertebrates. Hence, this study aimed at (1) examining the influence of the predation of hemipterans on the number of emerging adult mosquitoes and (2) detecting Anopheles mosquito DNA in the gut of those predators. The prey and predators were collected from a range of water bodies located in the Gilgel Gibe watershed, southwest Ethiopia. A semi-field study was carried out using mesocosms which were constructed using plastic containers mimicking the natural aquatic habitat of immature Anopheles mosquitoes. Adult mosquitoes that emerged from the mesocosms were collected using a mechanical aspirator. At the end of the experiment, predators were withdrawn from the mesocosms and identified to genus level. Polymerase Chain Reaction (PCR) was employed to identify sibling species of Anopheles gambiae s.l. and to detect Anopheles mosquito DNA in the gut of the predators. Data were analysed using R software. Giant water bugs (belostomatids) were the most aggressive predators of Anopheles larvae, followed by backswimmers (notonectids) and water boatmen (corixids). All female Anopheles gambiae s.l. emerged from the mesocosms were identified as Anopheles arabiensis. Anopheles arabiensis DNA was detected in the gut content of hemipteran specimens analysed from the three families. The number of the adult mosquitoes emerging from the mesocosms was affected by the presence of predators. The findings of this study provide evidence of the potential use of aquatic macroinvertebrate predators as biocontrol agents against immature Anopheles mosquitoes and their potential to be considered as a component of integrated vector management for insecticide resistance and the combined restoration of aquatic ecosystems via smart ecological engineering.
Dental Education during the COVID-19 Pandemic in a German Dental Hospital
Authors: Winter Julia , Frankenberger Roland , Günther Frank , Roggendorf Matthias Johannes
Published: June 2021

Due to the SARS-CoV-2 pandemic, dental treatment performed by undergraduate students at the University of Marburg/Germany was immediately stopped in spring 2020 and stepwise reinstalled under a new hygiene concept until full recovery in winter 2020/21. Patient treatment in the student courses was evaluated based on three aspects: (1) Testing of patients with a SARS-CoV-2 Rapid Antigen (SCRA) Test applied by student assistants (SA); (2) Improved hygiene regimen, with separated treatment units, cross-ventilation, pre-operative mouth rinse and rubber dam application wherever possible; (3) Recruitment of patients: 735 patients were pre-registered for the two courses; 384 patients were treated and a total of 699 tests with the SCRA test were performed by SAs. While half of the patients treated in the course were healthy, over 40% of the patients that were pre-registered but not treated in the course revealed a disease being relevant to COVID (p < 0.001). 46 patients had concerns to visit the dental hospital due to the increase of COVID incidence levels, 14 persons refused to be tested. The presented concept was suitable to enable patient treatment in the student course during the SARS-CoV-2 pandemic.
The Influence of Women’s Empowerment on Poverty Reduction in the Rural Areas of Bangladesh: Focus on Health, Education and Living Standard
Authors: Wei Wei , Sarker Tanwne , Żukiewicz-Sobczak Wioletta , Roy Rana , Alam G. M. Monirul , Rabbany Md. Ghulam , Hossain Mohammad Shakhawat , Aziz Noshaba
Published: June 2021

Women’s empowerment has a great influence on health, nutrition, education, and the overall well-being of societies as well as of the children and households. This study investigates the effect of women’s empowerment on poverty reduction and focuses on household deprivation, in terms of education, health, and standard of living. Primary data was collected from 914 married women from rural areas of Bangladesh using a well-structured questionnaire and a random sampling technique. Descriptive statistics, logistic regression, and ordinary least squares models were used in this study. The results indicate that increased women’s access to education, asset ownership, decision-making power on children’s health and education, and access to medical facilities, have caused a significant decline in income poverty and multidimensional poverty. However, gender violence, taking resources against women’s will, and preventing women from working outside, have caused a considerable decline in per capita income and an increase in income poverty and multidimensional poverty. Overall, it is found that women’s empowerment has a great impact on the reduction of income poverty and multidimensional poverty in society. The findings of the study can assist and guide policymakers to initiate appropriate strategies for women’s empowerment to reducing poverty in Bangladesh while making progress towards other social and developmental goals.
Randomized Controlled Trial of Simple Salt Reduction Instructions by Physician for Patients with Type 2 Diabetes Consuming Excessive Salt
Authors: Oyabu Chikako , Ushigome Emi , Ono Yuriko , Kobayashi Ayaka , Hashimoto Yoshitaka , Sakai Ryosuke , Iwase Hiroya , Okada Hiroshi , Yokota Isao , Tanaka Toru , Fukui Michiaki
Published: June 2021

Objectives: We verified the clinical usefulness of an approach method in which a physician gives simple salt reduction instructions during outpatient visits to patients with type 2 diabetes. Methods: This study was an open-blind, randomized controlled trial. Subjects were outpatients with type 2 diabetes whose estimated salt intake using spot morning urine sample exceeded the target of salt intake. The control group (CG) was notified only of the current salt intake, whereas the intervention group (IG) was given the brief salt reduction instruction by a physician in addition to the information regarding their current salt intake. Results: The change in estimated salt intake was −0.6 g (from 10.1 to 9.5 g, p = 0.029) in the CG after 8 weeks, and −0.9 g (from 10.1 to 9.2 g, p = 0.001) in the IG, although there were no significant differences between them (p = 0.47). After 24 weeks, both groups no longer differed significantly from the baseline. In addition, multivariate linear regression analyses indicated that high salt intake and low estimated glomerular filtration rate at baseline were significantly associated with salt reduction after 8 weeks. Conclusions: Salt-reducing effects were observed after 8 weeks in both the IG and CG, but no significant difference was observed. Moreover, patients with high salt intake and renal disfunction may be more effective in accepting salt reduction instructions. Making patients aware of the importance of salt reduction through a physician is effective for continuous salt reduction, and it is important to continue regular and repetitive guidance.
Quality-of-Life Determinants in People with Diabetes Mellitus in Europe
Authors: Fuentes-Merlos Álvaro , Orozco-Beltrán Domingo , Quesada Rico Jose A. , Reina Raul
Published: June 2021

This study aims to analyze self-perceived health and lifestyles in the European Union Member States Iceland, Norway, and the United Kingdom, examining associations with diabetes prevalence; and to identify the demographic, economic and health variables associated with diabetes in this population. We performed a cross-sectional study of 312,172 people aged 15 years and over (150,656 men and 161,516 women), using data collected from the European Health Interview Survey (EHIS). The EHIS includes questions on the health status and health determinants of the adult population, as well as health care use and accessibility. To estimate the magnitudes of the associations with diabetes prevalence, we fitted multivariate logistic models. The EHIS data revealed a prevalence of diabetes in Europe of 6.5% (n = 17,029). Diabetes was associated with being physically inactive (OR 1.14; 95% CI 1.02–1.28), obese (OR 2.75; 95% CI 2.60–2.90), male (OR 1.46; 95% CI 1.40–1.53) and 65–74 years old (OR 3.47; 95% CI 3.09–3.89); and having long-standing health problems (OR 7.39; 95% CI, 6.85–7.97). These results were consistent in the bivariate and multivariate analyses, with an area under the receiver operating characteristic curve of 0.87 (95% CI 0.87–0.88). In a large European health survey, diabetes was clearly associated with a poorer perceived quality of life, physical inactivity, obesity, and other comorbidities, as well as non-modifiable factors such as older age and male sex.
Assessment of Lead and Mercury Exposure Levels in the General Population of Korea Using Integrated National Biomonitoring Data
Authors: Seo Jeong-Wook , Hong Young-Seoub , Kim Byoung-Gwon
Published: June 2021

In Korea, the estimated values of blood lead (Pb) and mercury (Hg) levels differ between two national-level biomonitors, namely the Korean National Environmental Health Survey and the Korea National Health and Nutrition Examination Survey. The present study used integrated data from these surveys to estimate the representative values of the change in concentration and recent distribution characteristics. The yearly trend of age-standardized exposure levels in regular adults was identified, and the geometric mean (GM) adjusted according to demographic characteristics was presented. Age-standardized GM for blood Pb and Hg in the integrated data was 2.06 and 3.64 μg/L in 2008, respectively, which decreased to 1.55 and 2.92 μg/L, respectively, by 2017. Adjusted GMs from most recently conducted surveys (2015–2017) were 1.61 and 2.98 μg/L for blood Pb and Hg, respectively. In particular, the adjusted percentage of blood Hg exceeding the reference value of 5 μg/L was 20.79%. While the blood Pb and Hg exposure levels are decreasing in Korea, the levels remain high relative to those in other countries. The Hg levels exceeded the reference value in many individuals. Therefore, continued biomonitoring must be conducted, and a reduction plan and exposure management are needed for harmful metals, including Hg.
Acute Effects of Wearing Bite-Aligning Mouthguards on Muscular Strength, Power, Agility and Quickness in a Trained Population: A Systematic Review
Authors: Miró Adrià , Buscà Bernat , Aguilera-Castells Joan , Arboix-Alió Jordi
Published: June 2021

The purpose of the present systematic review was to determine the acute effects of wearing bite-aligning mouthguards on muscle strength, power, agility and quickness in athletes. A search of the current literature was performed using the electronic databases (until 1 May 2021) Web of Science, Scopus and Medline. The inclusion criteria were: (1) descriptive design studies; (2) with randomized clinical trials; (3) examining the within-subject acute effects of wearing mouthguards on functional and neuromuscular performance parameters; (4) in physical active, recreational or high-standard athletes. Twenty-seven studies met the inclusion criteria. Sixteen reported positive effects in some of the variables assessed, two reported negative effects and the rest found no significant differences. Overall, the main findings described in the literature are inconclusive concerning the neuromuscular advantages of using mouthguards in muscle strength, power, agility and quickness. These discrepancies might be related to several factors such as differences in testing protocols, poor control of the jaw magnitude and improper mouthguard designs. Despite these differences, after conducting the present systematic review, the authors speculate that jaw clenching while wearing custom-made, bite-aligning oral devices might promote beneficial effects in lower limb power actions, especially in jump ability and knee extension movements. Thus, athletes might consider the use of mouthguards, not only for their protective role but also for the potential ergogenic effects in specific actions, mainly those for which lower limb muscular power are required.
Gestational Diabetes Mellitus (GDM) Risk for Declared Family History of Diabetes, in Combination with BMI Categories
Authors: Lewandowska Małgorzata
Published: June 2021

Whether categories of family history of diabetes can act as independent risk factors for gestational diabetes mellitus (GDM-1, -2) has not yet been established, and neither has it been established how categories of body mass index (BMI) affect these relationships. A group of 912 women without chronic diseases, recruited in the first trimester, was investigated: 125 (13.7%) women developed GDM-1 (treated with diet); 21 (2.3%) women developed GDM-2 (treated with insulin); and a control group consisted of 766 non-diabetic women. A multiple logistic regression was used to evaluate adjusted odds ratios (AOR (95% confidence intervals)) of GDM-1 and GDM-2 for declared diabetes in the parents or grandparents (separately). These relationships were investigated in the whole cohort and subgroups of pre-pregnancy BMI. (1) Some categories of the family history were independent risk factors of GDM-1 or GDM-2. Compared to ‘absence of diabetes in the family’, women with diabetes in the father had a 3.68-fold increase in GDM-1 risk (AOR-b = 3.68 (2.23–6.07)), and women with diabetes in the mother had a 2.13-fold increase in GDM-1 risk (AOR-b = 2.13 (1.1–4.14)) and a 4.73-fold increase in GDM-2 risk (AOR-b = 4.73 (1.26–17.77)). Women with diabetes in the grandmother had a 2.34-fold increase in GDM-1 risk (AOR-b = 2.34 (1.29–4.24)). (2) The cumulative assessment of diabetes in the parents and/or grandparents was not related to the intensification of the risk of GDM, except for the increased risk of GDM-1 for diabetes in both mother and grandmothers simultaneously (AOR-b = 8.80 (1.16–66.57)), however, this group was very small. (3) The analyses in the subgroups of BMI categories showed that diabetes in the father was also an independent risk factor of GDM in the subgroup of pregnant women with normal BMI. In the subgroups of overweight and/or obesity, the risk of GDM for paternal and maternal diabetes was approximately twice as high as compared to the results of pregnant women with normal BMIs. Additionally, apart from the maternal influence of diabetes, the results suggest a significant influence of diabetes in the father on the risk of GDM, even (interestingly) in lean pregnant women.
Indoor Positioning Algorithm Based on Maximum Correntropy Unscented Information Filter
Authors: Ma Li , Cao Ning , Feng Xiaoliang , Mao Minghe
Published: June 2021

In view of the fact that indoor positioning systems are usually affected by non-Gaussian noise in complex indoor environments, this paper tests the data in the actual scene and analyzes the distribution characteristics of noise, and proposes a new indoor positioning algorithm based on maximum correntropy unscented information filter (MCUIF). The proposed indoor positioning algorithm includes three steps: First, the estimation of the state matrix and the corresponding covariance matrix are predicted through the unscented transformation (UT). Second, the observed information is reconstructed by using a nonlinear regression method on the basis of the maximum correntropy criterion (MCC). Third, the contribution of information vector is gained by non-Gaussian measurement and the predicted information vector is corrected by the contribution of information vector. Finally, the gain of information filtering is got by the information entropy state matrix and the information entropy measurement matrix to calculate the position coordinates of the unknown nodes. This algorithm enhances the robustness of the MCUIF to non-Gaussian noise in complex indoor environments. The results from the indoor positioning experiments show that MCUIF is better than the traditional methods in state estimation and position location of the unknown nodes.
Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases
Authors: Gaudel Fanny , Guiraudie-Capraz Gaëlle , Féron François
Published: June 2021

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.
Mesenchymal Stromal Cells Regulate Sialylations of N-Glycans, Affecting Cell Migration and Survival
Authors: Templeton Kayla , Ramos Meiby , Rose Jacqueline , Le Bryan , Zhou Qingwen , Cressman Amin , Ferreyra Stephanie , Lebrilla Carlito B. , Fierro Fernando Antonio
Published: June 2021

N-Glycosylations are an important post-translational modification of proteins that can significantly impact cell function. Terminal sialic acid in hybrid or complex N-glycans has been shown to be relevant in various types of cancer, but its role in non-malignant cells remains poorly understood. We have previously shown that the motility of human bone marrow derived mesenchymal stromal cells (MSCs) can be modified by altering N-glycoforms. The goal of this study was to determine the role of sialylated N-glycans in MSCs. Here, we show that IFN-gamma or exposure to culture media low in fetal bovine serum (FBS) increases sialylated N-glycans, while PDGF-BB reduces them. These stimuli alter mRNA levels of sialyltransferases such as ST3Gal1, ST6Gal1, or ST3Gal4, suggesting that sialylation of N-glycans is regulated by transcriptional control of sialyltransferases. We next show that 2,4,7,8,9-pentaacetyl-3Fax-Neu5Ac-CO2Me (3F-Neu5Ac) effectively inhibits sialylations in MSCs. Supplementation with 3F-Neu5Ac increases adhesion and migration of MSCs, as assessed by both videomicroscopy and wound/scratch assays. Interestingly, pre-treatment with 3F-Neu5Ac also increases the survival of MSCs in an in vitro ischemia model. We also show that pre-treatment or continuous treatment with 3F-Neu5Ac inhibits both osteogenic and adipogenic differentiation of MSCs. Finally, secretion of key trophic factors by MSCs is variably affected upon exposure to 3F-Neu5Ac. Altogether, our experiments suggest that sialylation of N-glycans is tightly regulated in response to environmental cues and that glycoengineering MSCs to reduce sialylated N-glycans could be beneficial to increase both cell migration and survival, which may positively impact the therapeutic potential of the cells.
Possible Crosstalk of the Immune Cells within the Lung and Mediastinal Fat-Associated Lymphoid Clusters in the Acute Inflammatory Lung Asthma-Like Mouse Model
Authors: Elewa Yaser Hosny Ali , Abd Elwakil Mahmoud Mansour , Ichii Osamu , Nakamura Teppei , Mohamed Sherif Kh. A. , Kon Yasuhiro
Published: June 2021

Recently, we clarified the function of mediastinal fat-associated lymphoid clusters (MFALCs) in the progression of several respiratory diseases. However, their role has not yet been identified in the lung asthmatic condition. Hence, we compared the immune cells in lung and MFALCs of C57BL/6N mice on days 3 and 7 following intranasal instillation of either papain (papain group “PG”) or phosphate buffer saline (PBS) (vehicle group “VG”). The PG showed significantly prominent MFALCs, numerous goblet cells (GCs), and higher index ratios of different immune cells (macrophages, natural helper cells (NHC), B- and T-lymphocytes) within the MFALCs and lung than in the VG on both days 3 and 7. Interestingly, a tendency of decreased size of MFALCs and a significant reduction in the number of GCs and immune cells were observed within the MFALCs and lung in the PG on day 7 than on day 3. Furthermore, the quantitative parameters of these immune cells in MFALCs were significantly and positively correlated with the size of MFALCs and immune cells in the lung. This suggested that the possible crosstalk between immune cells within MFALCs and the lung could play a critical role in the progression and recovery of the acute inflammatory lung asthma.
Therapeutic Targeting of the Leukaemia Microenvironment
Authors: Kuek Vincent , Hughes Anastasia M. , Kotecha Rishi S. , Cheung Laurence C.
Published: June 2021

In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia.
Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant N-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein
Authors: Lesnova Ekaterina I. , Masalova Olga V. , Permyakova Kristina Yu. , Kozlov Vyacheslav V. , Nikolaeva Tatyana N. , Pronin Alexander V. , Valuev-Elliston Vladimir T. , Ivanov Alexander V. , Kushch Alla A.
Published: June 2021

Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.
Hypoxia as a Stimulus for the Maturation of Meniscal Cells: Highway to Novel Tissue Engineering Strategies?
Authors: Herrera Millar Valentina Rafaela , Mangiavini Laura , Polito Umberto , Canciani Barbara , Nguyen Van Thi , Cirillo Federica , Anastasia Luigi , Peretti Giuseppe Maria , Modina Silvia Clotilde , Di Giancamillo Alessia
Published: June 2021

The meniscus possesses low self-healing properties. A perfect regenerative technique for this tissue has not yet been developed. This work aims to evaluate the role of hypoxia in meniscal development in vitro. Menisci from neonatal pigs (day 0) were harvested and cultured under two different atmospheric conditions: hypoxia (1% O2) and normoxia (21% O2) for up to 14 days. Samples were analysed at 0, 7 and 14 days by histochemical (Safranin-O staining), immunofluorescence and RT-PCR (in both methods for SOX-9, HIF-1α, collagen I and II), and biochemical (DNA, GAGs, DNA/GAGs ratio) techniques to record any possible differences in the maturation of meniscal cells. Safranin-O staining showed increments in matrix deposition and round-shape “fibro-chondrocytic” cells in hypoxia-cultured menisci compared with controls under normal atmospheric conditions. The same maturation shifting was observed by immunofluorescence and RT-PCR analysis: SOX-9 and collagen II increased from day zero up to 14 days under a hypoxic environment. An increment of DNA/GAGs ratio typical of mature meniscal tissue (characterized by fewer cells and more GAGs) was observed by biochemical analysis. This study shows that hypoxia can be considered as a booster to achieve meniscal cell maturation, and opens new opportunities in the field of meniscus tissue engineering.
Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach
Authors: Lozano Maria L. , Segú-Vergés Cristina , Coma Mireia , Álvarez-Roman María T. , González-Porras José R. , Gutiérrez Laura , Valcárcel David , Butta Nora
Published: June 2021

Eltrombopag is a thrombopoietin receptor (MPL) agonist approved for the treatment of primary immune thrombocytopenia (ITP). Recent evidence shows that some patients may sustain platelet counts following eltrombopag discontinuation. The systemic immunomodulatory response that resolves ITP in some patients could result from an increase in platelet mass, caused either by the direct action of eltrombopag on megakaryocytes through MPL stimulation, or potential MPL-independent actions on other cell types. To uncover the possible mechanisms of action of eltrombopag, in silico analyses were performed, including a systems biology-based approach, a therapeutic performance mapping system, and structural analyses. Through manual curation of the available bibliography, 56 key proteins were identified and integrated into the ITP interactome analysis. Mathematical models (94.92% mean accuracy) were obtained to elucidate potential MPL-dependent pathways in non-megakaryocytic cell subtypes. In addition to the effects on megakaryocytes and platelet numbers, the results were consistent with MPL-mediated effects on other cells, which could involve interferon-gamma, transforming growth factor-beta, peroxisome proliferator-activated receptor-gamma, and forkhead box protein P3 pathways. Structural analyses indicated that effects on three apoptosis-related proteins (BCL2L1, BCL2, BAX) from the Bcl-2 family may be off-target effects of eltrombopag. In conclusion, this study proposes new hypotheses regarding the immunomodulatory functions of eltrombopag in patients with ITP.
Biofilm Spreading by the Adhesin-Dependent Gliding Motility of Flavobacterium johnsoniae: 2. Role of Filamentous Extracellular Network and Cell-to-Cell Connections at the Biofilm Surface
Authors: Sato Keiko , Naya Masami , Hatano Yuri , Kasahata Naoki , Kondo Yoshio , Sato Mari , Takebe Katsuki , Naito Mariko , Sato Chikara
Published: June 2021

Flavobacterium johnsoniae forms a thin spreading colony on nutrient-poor agar using gliding motility. As reported in the first paper, WT cells in the colony were sparsely embedded in self-produced extracellular polymeric matrix (EPM), while sprB cells were densely packed in immature biofilm with less matrix. The colony surface is critical for antibiotic resistance and cell survival. We have now developed the Grid Stamp-Peel method whereby the colony surface is attached to a TEM grid for negative-staining microscopy. The images showed that the top of the spreading convex WT colonies was covered by EPM with few interspersed cells. Cells exposed near the colony edge made head-to-tail and/or side-to-side contact and sometimes connected via thin filaments. Nonspreading sprB and gldG and gldK colonies had a more uniform upper surface covered by different EPMs including vesicles and filaments. The EPM of sprB, gldG, and WT colonies contained filaments ~2 nm and ~5 nm in diameter; gldK colonies did not include the latter. Every cell near the edge of WT colonies had one or two dark spots, while cells inside WT colonies and cells in SprB-, GldG-, or GldK-deficient colonies did not. Together, our results suggest that the colony surface structure depends on the capability to expand biofilm.
PGC1s and Beyond: Disentangling the Complex Regulation of Mitochondrial and Cellular Metabolism
Authors: Coppi Lara , Ligorio Simona , Mitro Nico , Caruso Donatella , De Fabiani Emma , Crestani Maurizio
Published: June 2021

Metabolism is the central engine of living organisms as it provides energy and building blocks for many essential components of each cell, which are required for specific functions in different tissues. Mitochondria are the main site for energy production in living organisms and they also provide intermediate metabolites required for the synthesis of other biologically relevant molecules. Such cellular processes are finely tuned at different levels, including allosteric regulation, posttranslational modifications, and transcription of genes encoding key proteins in metabolic pathways. Peroxisome proliferator activated receptor γ coactivator 1 (PGC1) proteins are transcriptional coactivators involved in the regulation of many cellular processes, mostly ascribable to metabolic pathways. Here, we will discuss some aspects of the cellular processes regulated by PGC1s, bringing up some examples of their role in mitochondrial and cellular metabolism, and how metabolic regulation in mitochondria by members of the PGC1 family affects the immune system. We will analyze how PGC1 proteins are regulated at the transcriptional and posttranslational level and will also examine other regulators of mitochondrial metabolism and the related cellular functions, considering approaches to identify novel mitochondrial regulators and their role in physiology and disease. Finally, we will analyze possible therapeutical perspectives currently under assessment that are applicable to different disease states.
Activated Alpha-2 Macroglobulin Improves Insulin Response via LRP1 in Lipid-Loaded HL-1 Cardiomyocytes
Authors: Actis Dato Virginia , Chiabrando Gustavo Alberto
Published: June 2021

Activated alpha-2 Macroglobulin (α2M*) is specifically recognized by the cluster I/II of LRP1 (Low-density lipoprotein Receptor-related Protein-1). LRP1 is a scaffold protein for insulin receptor involved in the insulin-induced glucose transporter type 4 (GLUT4) translocation to plasma membrane and glucose uptake in different types of cells. Moreover, the cluster II of LRP1 plays a critical role in the internalization of atherogenic lipoproteins, such as aggregated Low-density Lipoproteins (aggLDL), promoting intracellular cholesteryl ester (CE) accumulation mainly in arterial intima and myocardium. The aggLDL uptake by LRP1 impairs GLUT4 traffic and the insulin response in cardiomyocytes. However, the link between CE accumulation, insulin action, and cardiac dysfunction are largely unknown. Here, we found that α2M* increased GLUT4 expression on cell surface by Rab4, Rab8A, and Rab10-mediated recycling through PI3K/Akt and MAPK/ERK signaling activation. Moreover, α2M* enhanced the insulin response increasing insulin-induced glucose uptake rate in the myocardium under normal conditions. On the other hand, α2M* blocked the intracellular CE accumulation, improved the insulin response and reduced cardiac damage in HL-1 cardiomyocytes exposed to aggLDL. In conclusion, α2M* by its agonist action on LRP1, counteracts the deleterious effects of aggLDL in cardiomyocytes, which may have therapeutic implications in cardiovascular diseases associated with hypercholesterolemia.
Evaluation of Firefly and Renilla Luciferase Inhibition in Reporter-Gene Assays: A Case of Isoflavonoids
Authors: Kenda Maša , Vegelj Jan , Herlah Barbara , Perdih Andrej , Mladěnka Přemysl , Sollner Dolenc Marija
Published: June 2021

Firefly luciferase is susceptible to inhibition and stabilization by compounds under investigation for biological activity and toxicity. This can lead to false-positive results in in vitro cell-based assays. However, firefly luciferase remains one of the most commonly used reporter genes. Here, we evaluated isoflavonoids for inhibition of firefly luciferase. These natural compounds are often studied using luciferase reporter-gene assays. We used a quantitative structure–activity relationship (QSAR) model to compare the results of in silico predictions with a newly developed in vitro assay that enables concomitant detection of inhibition of firefly and Renilla luciferases. The QSAR model predicted a moderate to high likelihood of firefly luciferase inhibition for all of the 11 isoflavonoids investigated, and the in vitro assays confirmed this for seven of them: daidzein, genistein, glycitein, prunetin, biochanin A, calycosin, and formononetin. In contrast, none of the 11 isoflavonoids inhibited Renilla luciferase. Molecular docking calculations indicated that isoflavonoids interact favorably with the D-luciferin binding pocket of firefly luciferase. These data demonstrate the importance of reporter-enzyme inhibition when studying the effects of such compounds and suggest that this in vitro assay can be used to exclude false-positives due to firefly or Renilla luciferase inhibition, and to thus define the most appropriate reporter gene.
Vitamin C—Protective Role in Oxidative Stress Conditions Induced in Human Normal Colon Cells by Label-Free Raman Spectroscopy and Imaging
Authors: Beton Karolina , Brozek-Pluska Beata
Published: June 2021

Colorectal cancer is the second most frequently diagnosed cancer worldwide. Conventional diagnostics methods of colorectal cancer can detect it at an advanced stage. Spectroscopic methods, including Raman spectroscopy and imaging, are becoming more and more popular in medical applications, and allow fast, precise, and unambiguous differentiation of healthy and cancerous samples. The most important advantage of Raman spectroscopy is the ability to identify biomarkers that help in the differentiation of healthy and cancerous cells based on biochemistry of sample and spectra typical for lipids, proteins, and DNA. The aim of the study was to evaluate the biochemical and structural features of human colon cell lines based on Raman spectroscopy and imaging: normal cells CCD-18 Co, normal cells CCD-18 Co under oxidative stress conditions, and normal cells CCD-18 Co at first treated by using tert-Butyl hydroperoxide and then supplemented by vitamin C in high concentration to show the protective role of vitamin C in micromolar concentrations against ROS (Reactive Oxygen Species). Raman data obtained for normal cells injured by ROS were compared with spectra typical for cancerous cells. Statistically assisted analysis has shown that normal ROS-injured and cancerous human colon cells can be distinguished based on their unique vibrational properties. The research carried out proves that label-free Raman spectroscopy may play an important role in clinical diagnostics differentiation of normal and cancerous colon cells and may be a source of intraoperative information supporting histopathological analysis.
Impact of P2X7 Purinoceptors on Goblet Cell Function: Implications for Dry Eye
Authors: Puro Donald G.
Published: June 2021

By providing ~70% of the eye’s refractive power, the preocular tear film is essential for optimal vision. However, its integrity is often jeopardized by environmental and pathologic conditions that accelerate evaporation and cause sight-impairing dry eye. A key adaptive response to evaporation-induced tear film hyperosmolarity is the reflex-triggered release of tear-stabilizing mucin from conjunctival goblet cells. Here, we review progress in elucidating the roles of ion channels in mediating this important exocytotic response. Much is now known about the modulatory impact of ATP-sensitive potassium channels, nonspecific cation channels and voltage-gated calcium channels. Recently, we discovered that during unremitting extracellular hyperosmolarity, P2X7 receptor/channels also become activated and markedly impair goblet cell viability. However, our understanding of possible adaptive benefits of this P2X7 activation remains limited. In the present study, we utilized high-temporal resolution membrane capacitance measurements to monitor the exocytotic activity of single goblet cells located in freshly excised rat conjunctiva. We now report that activation of P2X7 purinoceptors boosts neural-evoked exocytosis and accelerates replenishment of mucin-filled granules after exocytotic depletion. Thus, P2X7 activation exerts a yin-yang effect on conjunctival goblet cells: the high-gain benefit of enhancing the supply of tear-stabilizing mucin is implemented at the high-risk of endangering goblet cell survival.
Stage-Specific Characterization of Physiological Response to Heat Stress in the Wheat Cultivar Norin 61
Authors: Matsunaga Sachiko , Yamasaki Yuji , Toda Yusuke , Mega Ryosuke , Akashi Kinya , Tsujimoto Hisashi
Published: June 2021

Bread wheat (Triticum aestivum) is less adaptable to high temperatures than other major cereals. Previous studies of the effects of high temperature on wheat focused on the reproductive stage. There are few reports on yield after high temperatures at other growth stages. Understanding growth-stage-specific responses to heat stress will contribute to the development of tolerant lines suited to high temperatures at various stages. We exposed wheat cultivar “Norin 61” to high temperature at three growth stages: seedling–tillering (GS1), tillering–flowering (GS2), and flowering–maturity (GS3). We compared each condition based on agronomical traits, seed maturity, and photosynthesis results. Heat at GS2 reduced plant height and number of grains, and heat at GS3 reduced the grain formation period and grain weight. However, heat at GS1 reduced senescence and prolonged grain formation, increasing grain weight without reducing yield. These data provide fundamental insights into the biochemical and molecular adaptations of bread wheat to high-temperature stresses and have implications for the development of wheat lines that can respond to high temperatures at various times of the year.
Targeting Intra-Pulmonary P53-Dependent Long Non-Coding RNA Expression as a Therapeutic Intervention for Systemic Lupus Erythematosus-Associated Diffuse Alveolar Hemorrhage
Authors: Chen Yi-Cheng , Chou Yu-Chi , Hsieh Yu-Tung , Kuo Pin-Yu , Yang Mei-Lin , Chong Hao-Earn , Wu Chao-Liang , Shiau Ai-Li , Wang Chrong-Reen
Published: June 2021

Diffuse alveolar hemorrhage (DAH) in systemic lupus erythematosus (SLE) is associated with significant mortality, requiring a thorough understanding of its complex mechanisms to develop novel therapeutics for disease control. Activated p53-dependent apoptosis with dysregulated long non-coding RNA (lncRNA) expression is involved in the SLE pathogenesis and correlated with clinical activity. We examined the expression of apoptosis-related p53-dependent lncRNA, including H19, HOTAIR and lincRNA-p21 in SLE-associated DAH patients. Increased lincRNA-p21 levels were detected in circulating mononuclear cells, mainly in CD4+ and CD14+ cells. Higher expression of p53, lincRNA-p21 and cell apoptosis was identified in lung tissues. Lentivirus-based short hairpin RNA (shRNA)-transduced stable transfectants were created for examining the targeting efficacy in lncRNA. Under pristane stimulation, alveolar epithelial cells had increased p53, lincRNA-p21 and downstream Bax levels with elevated apoptotic ratios. After pristane injection, C57/BL6 mice developed DAH with increased pulmonary expression of p53, lincRNA-p21 and cell apoptosis. Intra-pulmonary delivery of shRNA targeting lincRNA-p21 reduced hemorrhage frequencies and improved anemia status through decreasing Bax expression and cell apoptosis. Our findings demonstrate increased p53-dependent lncRNA expression with accelerated cell apoptosis in the lungs of SLE-associated DAH patients, and show the therapeutic potential of targeting intra-pulmonary lncRNA expression in a pristane-induced model of DAH.