bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro- and Macroelements Content of Plants Used for Landfill Leachate Treatment Based on Phragmites australis and Ceratophyllum demersum
Authors: Wdowczyk Aleksandra , Szymańska-Pulikowska Agata
Published: May 2022

One of the key problems associated with the functioning of landfills is the generation of leachate. In order to reduce their negative impact on the environment, various treatment technologies are applied. Among them, solutions based on the use of phytotechnology deserve special attention. The aim of this study was to evaluate the impact of landfill leachate on the content of micro- and macroelements in plant material. The research was carried out in four municipal waste landfills located in Poland. Emergent macrophytes (P. australis) and submergent macrophytes (C. demersum) were used in this research. The migration and distribution of pollutants reaching the roots and shoots of P. australis from water solutions were also studied. The concentrations of heavy metals in the studied plants were low in all analysed cases. Higher metal contents could often be observed in roots rather than in shoots, but these differences were insignificant. The chemical composition of the studied plant samples was primarily related to the source of origin of the treated leachate (landfill), as clearly demonstrated by cluster analysis. In the conducted studies, no important differences were noted in the accumulation of the studied components between submergent plants (C. demersum) and emergent macrophytes (P. australis).
The Determination of Radon/Thoron Exhalation Rate in an Underground Coal Mine—Preliminary Results
Authors: Bonczyk Michał , Chałupnik Stanisław , Wysocka Malgorzata , Grygier Agata , Hildebrandt Robert , Tosheva Zornitza
Published: May 2022

The objective of this work was to perform a series of measurements of radon and thoron exhalation in the underground workings of an experimental coal mine. In the years 2012–2015, experiments on underground coal gasification were carried out in a coal mine, which caused, among other effects, damage to rock mass. Afterward, periodic increases in the concentration of potential alpha energy (PAEC) of radon decay products in the air were found, which could pose a hazard to miners. The question posed was whether the gasification experiment resulted in the increased migration of radon and thoron. If so, did it increase the radiation hazard to miners? The adaptation of the existing instrumentation to the specific conditions was conducted, and a series of measurements were made. It was found that the measured values of radon and thoron exhalation rates ranged from 3.0 up to 38 Bq·m−2·h−1 for radon and from 500 up to 2000 Bq·m−2·h−1 for thoron.
Human Resources in Primary Health-Care Institutions before and after the New Health-Care Reform in China from 2003 to 2019: An Interrupted Time Series Analysis
Authors: Qin Chenyuan , Liu Min , Guo Xin , Liu Jue
Published: May 2022

At the end of March 2009, the Chinese government put forward the new health-care reform with its long-term goal to achieve universal access to basic medical and health services. Primary health-care institutions and adequate health human resources are the basic and specific guarantee to achieve the above goals. We aimed to explore the differences in the trends of human resources before and after the new health-care reform from 2003 to 2019, based on Chinese Health Statistics Yearbook, an using interrupted time series analysis. The number of primary health workers serving for every 1000 people in China gradually rose from 1.98 in 2003 to 3.07 in 2020, with an immediate sharp rise from 2008 to 2009. Subsequently, the number of primary health workers increased at a significant speed, but it still failed to meet people’s basic medical needs (3.5/1000). There was an increase of 51,301 primary health staff in 2010, and 6007 more primary health workers per year were added after the reform compared to the basic increasing number before 2009, but both were not statistically significant (p > 0.05). The annual increased number of health workers in township health centers was 2.63 times greater than that before the reform, with a total annual increase of 34,192 people (p < 0.05). The growth trend changed the most in western China (p < 0.001), while the human resources of primary health-care institutions in the eastern region were relatively richer than those in the central and western regions. Numerous registered nurses and pharmacists have been devoted to the construction of the primary health-care service since 2010, while the increase in the number of doctors per year was not statistically significant (p = 0.066). In total, the primary health-care human resource in China is constantly expanding, but the primary health-care needs are still not fully met, especially for doctors, and the problem of unbalanced allocation urgently needs to be solved. Reasonably formulating regional policies to strengthen the construction of primary health personnel and expand the accessibility of primary health services is the top priority in the development of primary medical and health undertakings.
Language Intervention in Down Syndrome: A Systematic Literature Review
Authors: Moraleda-Sepúlveda Esther , López-Resa Patricia , Pulido-García Noelia , Delgado-Matute Soraya , Simón-Medina Natalia
Published: May 2022

Language is one of the most affected areas in people with Down syndrome and is one of the most influential throughout their development. That is why the linguistic difficulties presented by this group are susceptible to treatment through different specific interventions. However, little emphasis has been placed on the effectiveness and importance of this type of intervention in improving their language skills. Therefore, this work aimed to carry out a systemic literature review of language intervention programs that have been carried out in the last 20 years. To this end, a total of 18 articles were analyzed in which the effectiveness of different types of treatment related to oral language, written language and communication, in general, was studied, using the guidelines of the PRISMA Statement and the COSMIN methodology. The results highlight that language intervention improves linguistic levels in people with Down Syndrome. Most of the research focuses on early interventions and interventions carried out through individual sessions. Nevertheless, the data are unanimous in considering the efficacy and effectiveness of the proposed treatments for improving the language skills of people with Down syndrome. Thus, linguistic intervention is a fundamental area of work throughout the lives of people with Down syndrome.
Research on the Design Strategy of Healing Products for Anxious Users during COVID-19
Authors: Wu Fan , Lin Yang-Cheng , Lu Peng
Published: May 2022

With the spread of COVID-19 worldwide, various travel restrictions are becoming a significant trigger for anxiety. Although healing products could relieve anxiety, few scholars have proposed a practical design strategy. Therefore, we offer a design strategy for healing products that includes three phases: preparation, analysis, and verification. In Phase 1, 20 people with moderate or high anxiety are invited to rate 100 samples. Then, FCM is used to obtain representative samples. In Phase 2, a three-layer diagram (incl. the upper, middle, and lower layers) of healing products is obtained using the evaluation grid method. Subsequently, the middle layer is considered evaluation criteria. Additionally, 18 items in the lower layer are considered design guidelines. In Phase 3, we invite two teams to develop innovative designs based on design guidelines and personal experience, generating four alternatives. Finally, four alternatives and four healing commodities are evaluated using grey relation analysis and perceptual questionnaires. The consistency of both evaluations could confirm the validity of the evaluation criteria. The alternatives generated based on the design guidelines are better than other alternatives, demonstrating the effectiveness of the design guidelines. The design strategy is beneficial for developing and evaluating healing products to alleviate people’s anxiety during COVID-19.
Forecasting of Flash Floods Peak Flow for Environmental Hazards and Water Harvesting in Desert Area of El-Qaa Plain, Sinai
Authors: Abd-Elaty Ismail , Shoshah Hanan , Zeleňáková Martina , Kushwaha Nand Lal , El-Dean Osama W.
Published: May 2022

Water resources in arid and semi-arid regions are limited where the demands of agriculture, drinking and industry are increasing, especially in drought areas. These regions are subjected to climate changes (CC) that affect the watershed duration and water supplies. Estimations of flash flooding (FF) volume and discharge are required for future development to meet the water demands in these water scarcity regions. Moreover, FF in hot deserts is characterized by low duration, high velocity and peak discharge with a large volume of sediment. Today, the trends of flash flooding due to CC have become very dangerous and affect water harvesting volume and human life due to flooding hazards. The current study forecasts the peak discharges and volumes in the desert of El-Qaa plain in Southwestern Sinai, Egypt, for drought and wet seasons by studying the influence of recurrence intervals for 2, 5, 10, 25, 50 and 100 years. Watershed modeling system software (WMS) is used and applied for the current study area delineation. The results show that the predictions of peak discharges reached 0, 0.44, 45.72, 195.45, 365.91 and 575.30 cubic meters per s (m3 s−1) while the volumes reached 0, 23, 149.80, 2,896,241.40, 12,664,963.80 and 36,681,492.60 cubic meters (m3) for 2, 5, 10, 25, 50 and 100 years, respectively, which are precipitation depths of 15.20, 35.30, 50.60, 70.70, 85.90 and 101 mm, respectively. Additionally, the average annual precipitation reached 13.37 mm, with peak flow and volume reaching 0 m3 s−1 where all of water harvesting returned losses. Moreover, future charts and equations were developed to estimate the peak flow and volume, which are useful for future rainwater harvesting and the design of protection against flooding hazards in drought regions due to CC for dry and wet seasons. This study provides relevant information for hazard and risk assessment for FF in hot desert regions. The study recommends investigating the impact of recurrence intervals on sediment transport in these regions.
Health Information Sources Influencing Health Literacy in Different Social Contexts across Age Groups in Northern Thailand Citizens
Authors: Buawangpong Nida , Sirikul Wachiranun , Anukhro Chanya , Seesen Mathuramat , La-up Aroon , Siviroj Penprapa
Published: May 2022

Health literacy is an essential social determinant of health and has been associated with positive health outcomes. While many sources of health information are widely available, people of different ages also have diverse social contexts and preferences for health information sources. This study aimed to identify health information sources and socio-demographics influencing health literacy in different social contexts across age groups: 15–29 years (young), 30–59 years (middle-age), and ≥60 years (elderly). We obtained secondary data from a cross-sectional study in northern Thailand from March to August 2019. Multivariate linear regression with age group subgroup analysis was used to determine factors associated with general health literacy by the Thai version of the health literacy questionnaire. Receiving health information from physicians was significantly associated with higher general health literacy in young (β 6.45, 95%CI 0.44–12.45; p = 0.035) and elderly (β 5.18, 95%CI 1.84–8.52; p = 0.002) groups, while receiving health information from health volunteers was significantly associated with a higher general health literacy in the middle-aged (β 2.89, 95%CI 0.38–5.39; p = 0.024) group. Although younger participants showed more frequent access to health information via the media than the other age groups, there were no media sources significantly linked with their general health literacy. Health information from physicians is a vital source of health information.
Understanding the Heterogeneous Impact of Innovation Efficiency on Urban Ecological Footprint in China
Authors: Zhang Hui , Ke Haiqian
Published: May 2022

Under the background of tightening resource constraints and a deteriorating ecological environment, innovation is aimed at saving energy, reducing consumption, abating pollution and achieving sustainable economic growth. This has gradually become an important way to improve industrial structure, competitiveness and environmental performance worldwide. In this study, we use the super-efficiency SBM model to calculate the innovation efficiency of 283 cities in China from 2009 to 2019. Then, based on the dynamic threshold regression model, we explore the impact of innovation efficiency on ecological footprint in innovative cities or non-innovative cities under different economic development levels. The main conclusions that can be drawn are as follows. (1) Within the research period, the influence of innovation efficiency on ecological footprint in China shows a negative double threshold feature, that is, increasing regional innovation efficiency has an inhibitory effect on ecological footprint. (2) For innovative cities, innovation efficiency has a strong inhibitory effect on ecological footprint, and it becomes stronger and stronger with the growth of night light data; but this inhibitory effect is gradually decreasing with improvement of economic development level in non-innovative cities. (3) Under the threshold of different levels of economic development, the number of scientific human resources, scientific financial resources, scientific information resources and scientific papers has a positive effect on ecological footprint, while the number of patent applications has a negative effect on ecological footprint.
Experimental Studies to Test a Predictive Indoor Radon Model
Authors: Mancini Simona , Vilnitis Martins , Todorović Nataša , Nikolov Jovana , Guida Michele
Published: May 2022

The accumulation of the radioactive gas radon in closed environments, such as dwellings, is the result of a quite complex set of processes related to the contribution of different sources. As it undergoes different physical mechanisms, all occurring at the same time, models describing the general dynamic turns out to be difficult to apply because of the dependence on many parameters not easy to measure or calculate. In this context, the authors developed, in a previous work, a simplified approach based on the combination of a physics-mathematical model and on-site experimental measurements. Three experimental studies were performed in order to preliminarily test the goodness of the model to simulate indoor radon concentrations in closed environments. In this paper, an application on a new experimental site was realized in order to evaluate the adaptability of the model to different house typologies and environmental contexts. Radon activity measurements were performed using a portable radon detector and results, showing again good performance of the model. Results are discussed and future efforts are outlined for the refining and implementation of the model into software.
Exploring Usability and Patient Attitude towards a Smart Hospital Service with the Technology Acceptance Model
Authors: Tu Jui-Che , Luo Shi Chen , Lee Yi-Lin , Shih Ming-Feng , Chiu Shu-Ping
Published: May 2022

The demand for health care has increased with the development of global technology and the rise of public health awareness, and smart service systems have also been introduced to medical care to relieve the pressure on hospital staff. However, the survey found that patients’ willingness to use smart services at the time of consultation has not improved. The main research purpose of this study was to understand the willingness of patients from various groups to use smart medical service systems and to explore the influencing factors on patients’ use of smart service systems in hospitals through the technology acceptance model. This study distributed questionnaires in the outpatient area of National Taiwan University Hospital Yunlin Branch, and a total of 202 valid questionnaires were obtained. After related research and regression analysis, it was found that patients paid more attention to the benefits and convenience brought by smart services. If patients believed that smart services were trustworthy and beneficial to themselves, their usage intention and attitude would be positive. The results of this study are summarized by the following four points: (1) Designed according to the cultural conditions of different regions; (2) think about design from the patient’s perspective; (3) strengthen the explanation and promotion of smart services; and (4) add humanized care and design. This study could be used as a reference for hospitals to improve their service quality and systems in the future.
Are All Urban Parks Robust to the COVID-19 Pandemic? Focusing on Type, Functionality, and Accessibility
Authors: Sung Hyungun , Kim Woo-Ram , Oh Jiyeon , Lee Samsu , Lee Peter Sang-Hoon
Published: May 2022

Many people visited urban parks during the COVID-19 pandemic to reduce the negative effects of lack of physical activity, social isolation, anxiety, and depression. It is unclear whether all parks are robust against the pandemic, helping people sustain healthy daily living through the diverse activities within them. Nevertheless, few studies have identified the specific relationship between park visits and the COVID-19 pandemic. Therefore, this study aims to demonstrate how physical features such as type, functionality, and access influenced daily visiting to parks during the pandemic, using mobile phone data at a micro level. This study first classified urban parks as point-type parks with an area of less than 1 ha, plane-type parks with 1 ha or more, and line-type parks with elongated shapes, while measuring accessibility to residential, employment, transportation, and auxiliary facilities within the park. The study employed the multi-level regression model with random intercept to investigate the effects of differing park visits, focusing on Goyang city, South Korea. Our analysis results identified that easy access from home was more important than the park size during the pandemic. If we look at the types of parks, the use of both plane- and point-type parks increased more than that of line-type parks. However, line-type parks near homes, along with shopping and sports facilities, were found to be more robust to the pandemic. These findings can be informative to provide specific guidelines to fulfill the enhanced role of parks in sustaining public health during an infectious disease pandemic that may strike again.
Prolonged Activation of Brain CB2 Signaling Modulates Hypothalamic Microgliosis and Astrogliosis in High Fat Diet-Fed Mice
Authors: Rorato Rodrigo , Ferreira Nathalia L. , Oliveira Franciane P. , Fideles Higor J. , Camilo Tays A. , Antunes-Rodrigues Jose , Mecawi Andre S. , Elias Lucila L. K.
Published: May 2022

Low-grade inflammation of the hypothalamus is associated with the disturbance of energy balance. The endocannabinoid system has been implicated in the development and maintenance of obesity as well as in the control of immune responses. The type 2 cannabinoid receptor (CB2) signaling has been associated with anti-inflammatory effects. Therefore, in high fat diet (HFD)-induced obese mice, we modulated CB2 signaling and investigated its effects on energy homeostasis and hypothalamic microgliosis/astrogliosis. We observed no effect on caloric intake and body weight gain in control diet-fed animals that received prolonged icv infusion of the CB2 receptor agonist HU308. Interestingly, we observed a decrease in glucose tolerance in HFD-fed animals treated with HU308. Prolonged icv infusion of HU308 increases astrogliosis in the ventromedial nucleus (VMH) of obese animals and reduced HFD-induced microgliosis in the hypothalamic arcuate (ARC) but not in the paraventricular (PVN) or VMH nuclei. These data indicate that central CB2 signaling modulates glucose homeostasis and glial reactivity in obesogenic conditions, irrespective of changes in body weight.
GPR37 Receptors and Megalencephalic Leukoencephalopathy with Subcortical Cysts
Authors: Pla-Casillanis Adrià , Ferigle Laura , Alonso-Gardón Marta , Xicoy-Espaulella Efren , Errasti-Murugarren Ekaitz , Marazziti Daniela , Estévez Raúl
Published: May 2022

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy (white matter disorder), which is mainly caused by defects in MLC1 or glial cell adhesion molecule (GlialCAM) proteins. In addition, autoantibodies to GlialCAM are involved in the pathology of multiple sclerosis. MLC1 and GLIALCAM genes encode for membrane proteins of unknown function, which has been linked to the regulation of different ion channels and transporters, such as the chloride channel VRAC (volume regulated anion channel), ClC-2 (chloride channel 2), and connexin 43 or the Na+/K+-ATPase pump. However, the mechanisms by which MLC proteins regulate these ion channels and transporters, as well as the exact function of MLC proteins remain obscure. It has been suggested that MLC proteins might regulate signalling pathways, but the mechanisms involved are, at present, unknown. With the aim of answering these questions, we have recently described the brain GlialCAM interactome. Within the identified proteins, we could validate the interaction with several G protein-coupled receptors (GPCRs), including the orphan GPRC5B and the proposed prosaposin receptors GPR37L1 and GPR37. In this review, we summarize new aspects of the pathophysiology of MLC disease and key aspects of the interaction between GPR37 receptors and MLC proteins.
Molecular Research on Platelet Activity in Health and Disease 3.0
Authors: Catani Maria Valeria , Savini Isabella , Gasperi Valeria
Published: May 2022

Zhao and Devine [...]
Exercise Normalized the Hippocampal Renin-Angiotensin System and Restored Spatial Memory Function, Neurogenesis, and Blood-Brain Barrier Permeability in the 2K1C-Hypertensive Mouse
Authors: Chang Ying-Shuang , Lin Chih-Lung , Lee Chu-Wan , Lin Han-Chen , Wu Yi-Ting , Shih Yao-Hsiang
Published: May 2022

Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.
Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer
Authors: Xue Nina , Du Tingting , Lai Fangfang , Jin Jing , Ji Ming , Chen Xiaoguang
Published: May 2022

The extracellular heat shock protein 90α (eHSP90α) has been reported to promote cancer cell motility. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α, as well as its underlying mechanism for PC progression, were still unclear. Our study demonstrated that the amounts of secreted HSP90α proteins were discrepant in multiple PC cells. In addition, highly invasive Capan-2 cells have a higher level of secreted HSP90α compared with those of less invasive PL45 cells. The conditioned medium of Capan-2 cells or recombinant HSP90α treatment stimulated the migration and invasion of PC cells, which could be prevented with a neutralizing anti-HSP90α antibody. Furthermore, secreted HSP90α promoted elements of epithelial–mesenchymal transition in PL45 cells, including increases in vimentin and Snail expressions, decreases in E-cadherin expression, and changes in cell shape towards a mesenchymal phenotype, but these phenomena were reversed by the anti-HSP90α antibody in Capan-2 cells. In addition, high levels of low-density lipoprotein receptor-related protein 1 (LRP1) were associated with worsened patient survival in pancreatic adenocarcinoma. We demonstrated LRP1 as a receptor of eHSP90α for its stimulatory role in metastasis, by activating the AKT pathway. In addition, silencing LRP1 enhanced the chemosensitivity to gemcitabine and doxorubicin in Capan-2 cells. Therefore, our study indicated that blocking secreted HSP90α underlies an aspect of metastasis and chemoresistance in PC.
Development of a Novel Anti−CD44 Monoclonal Antibody for Multiple Applications against Esophageal Squamous Cell Carcinomas
Authors: Goto Nohara , Suzuki Hiroyuki , Tanaka Tomohiro , Asano Teizo , Kaneko Mika K. , Kato Yukinari
Published: May 2022

CD44 is a cell surface glycoprotein, which is expressed on normal cells, and overexpressed on cancer cells. CD44 is involved in cell adhesion, migration, proliferation, survival, stemness, and chemo−resistance. Therefore, CD44 is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti−CD44 monoclonal antibodies (mAbs) by immunizing mice with a CD44 variant (CD44v3−10) ectodomain and screening using enzyme−linked immunosorbent assay. We then characterized them using flow cytometry, Western blotting, and immunohistochemistry. One of the established clones (C44Mab−46; IgG1, kappa) reacted with CD44 standard isoform (CD44s)−overexpressed Chinese hamster ovary−K1 cells (CHO/CD44s) or esophageal squamous cell carcinoma (ESCC) cell lines (KYSE70 and KYSE770). The apparent KD of C44Mab−46 for CHO/CD44s, KYSE70, and KYSE770 was 1.1 × 10−8 M, 4.9 × 10−8 M, and 4.1 × 10−8 M, respectively. C44Mab−46 detected CD44s of CHO/CD44s and KYSE70, and CD44 variants of KYSE770 in Western blot analysis. Furthermore, C44Mab−46 strongly stained the formalin−fixed paraffin−embedded ESCC tissues in immunohistochemistry. Collectively, C44Mab−46 is very useful for detecting CD44 in various applications.
The Promises of Natural Killer Cell Therapy in Endometriosis
Authors: Hoogstad-van Evert Janneke , Paap Romy , Nap Annemiek , van der Molen Renate
Published: May 2022

Endometriosis is a gynaecological disease defined by the growth of endometrium-like tissue outside the uterus. The disease is present in approximately 5–10% of women of reproductive age and causes pelvic pain and infertility. The pathophysiology is not completely understood, but retrograde menstruation and deficiency in natural killer (NK) cells that clear endometriotic cells in the peritoneal cavity play an important role. Nowadays, hormonal therapy and surgery to remove endometriosis lesions are used as treatment. However, these therapies do not work for all patients, and hormonal therapy prevents patients from getting pregnant. Therefore, new treatment strategies should be developed. Since the cytotoxicity of NK cells is decreased in endometriosis, we performed a literature search into the possibility of NK cell therapy. Available treatment options include the inhibition of receptor–ligand interaction for KIR2DL1, NKG2A, LILRB1/2, and PD-1/PD-L1; inhibition of TGF-β; stimulation of NK cells with IL-2; and mycobacterial treatment with BCG. In preclinical work, these therapies show promising results but unfortunately have side effects, which have not specifically been studied in endometriosis patients. Before NK cell treatment can be used in the clinic, more research is needed.
Osteoimmunology in Periodontitis: Local Proteins and Compounds to Alleviate Periodontitis
Authors: Sirisereephap Kridtapat , Maekawa Tomoki , Tamura Hikaru , Hiyoshi Takumi , Domon Hisanori , Isono Toshihito , Terao Yutaka , Maeda Takeyasu , Tabeta Koichi
Published: May 2022

Periodontitis is one of the most common oral diseases resulting in gingival inflammation and tooth loss. Growing evidence indicates that it results from dysbiosis of the oral microbiome, which interferes with the host immune system, leading to bone destruction. Immune cells activate periodontal ligament cells to express the receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL) and promote osteoclast activity. Osteocytes have active roles in periodontitis progression in the bone matrix. Local proteins are involved in bone regeneration through functional immunological plasticity. Here, we discuss the current knowledge of cellular and molecular mechanisms in periodontitis, the roles of local proteins, and promising synthetic compounds generating a periodontal regeneration effect. It is anticipated that this may lead to a better perception of periodontitis pathophysiology.
Ipsilateral and Contralateral Interactions in Spinal Locomotor Circuits Mediated by V1 Neurons: Insights from Computational Modeling
Authors: Shevtsova Natalia A. , Li Erik Z. , Singh Shayna , Dougherty Kimberly J. , Rybak Ilya A.
Published: May 2022

We describe and analyze a computational model of neural circuits in the mammalian spinal cord responsible for generating and shaping locomotor-like oscillations. The model represents interacting populations of spinal neurons, including the neurons that were genetically identified and characterized in a series of previous experimental studies. Here, we specifically focus on the ipsilaterally projecting V1 interneurons, their possible role in the spinal locomotor circuitry, and their involvement in the generation of locomotor oscillations. The proposed connections of these neurons and their involvement in different neuronal pathways in the spinal cord allow the model to reproduce the results of optogenetic manipulations of these neurons under different experimental conditions. We suggest the existence of two distinct populations of V1 interneurons mediating different ipsilateral and contralateral interactions within the spinal cord. The model proposes explanations for multiple experimental data concerning the effects of optogenetic silencing and activation of V1 interneurons on the frequency of locomotor oscillations in the intact cord and hemicord under different experimental conditions. Our simulations provide an important insight into the organization of locomotor circuitry in the mammalian spinal cord.
Sildenafil-Induced Revascularization of Rat Hindlimb Involves Arteriogenesis through PI3K/AKT and eNOS Activation
Authors: Baron-Menguy Celine , Bocquet Arnaud , Richard Alexis , Guihot Anne-Laure , Toutain Bertrand , Pacaud Pierre , Fassot Celine , Loirand Gervaise , Henrion Daniel , Loufrani Laurent
Published: May 2022

Hypoxia and inflammation play a major role in revascularization following ischemia. Sildenafil inhibits phosphodiesterase-5, increases intracellular cGMP and induces revascularization through a pathway which remains incompletely understood. Thus, we investigated the effect of sildenafil on post-ischemic revascularization. The left femoral artery was ligated in control and sildenafil-treated (25 mg/kg per day) rats. Vascular density was evaluated and expressed as the left/right leg (L/R) ratio. In control rats, L/R ratio was 33 ± 2% and 54 ± 9%, at 7- and 21-days post-ligation, respectively, and was significantly increased in sildenafil-treated rats to 47 ± 4% and 128 ± 11%, respectively. A neutralizing anti-VEGF antibody significantly decreased vascular density (by 0.48-fold) in control without effect in sildenafil-treated animals. Blood flow and arteriolar density followed the same pattern. In the ischemic leg, HIF-1α and VEGF expression levels increased in control, but not in sildenafil–treated rats, suggesting that sildenafil did not induce angiogenesis. PI3-kinase, Akt and eNOS increased after 7 days, with down-regulation after 21 days. Sildenafil induced outward remodeling or arteriogenesis in mesenteric resistance arteries in association with eNOS protein activation. We conclude that sildenafil treatment increased tissue blood flow and arteriogenesis independently of VEGF, but in association with PI3-kinase, Akt and eNOS activation.
Heterologous Expression of Dehydration-Inducible MfbHLH145 of Myrothamnus flabellifoli Enhanced Drought and Salt Tolerance in Arabidopsis
Authors: Huang Zhuo , Jin Si-Han , Yang Li , Song Li , Wang Yuan-Hong , Jian Lin-Li , Jiang Cai-Zhong
Published: May 2022

Myrothamnus flabellifolia is the only woody resurrection plant found in the world. It has a strong tolerance to drought and can survive long-term exposure to desiccated environments. However, few genes related to its drought tolerance have been functionally characterized and the molecular mechanisms underlying the stress tolerance of M. flabellifolia are largely unknown. In this study, we isolated a dehydration-inducible bHLH transcription factor gene MfbHLH145 from M. flabellifolia. Heterologous expression of MfbHLH145 enhanced the drought and salt tolerance of Arabidopsis. It can not only promote root system development under short-term stresses, but also improve growth performance under long-term treatments. Further investigation showed that MfbHLH145 contributes to enhanced leaf water retention capacity through the promotion of stomatal closure, increased osmolyte accumulation, and decreased stress-induced oxidative damage through an increase in antioxidant enzyme activities. These results suggest that MfbHLH145 may be involved in the positive regulation of stress responses in M. flabellifolia. This study provides insight into the molecular mechanism underlying the survival of M. flabellifolia in extreme dehydration conditions.
Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22 Exhibit Anti-Inflammatory Effect by Attenuation of NF-κB and MAPK Signaling in Human Bronchial Epithelial Cells
Authors: Stankovic Marija , Veljovic Katarina , Popovic Nikola , Kojic Snezana , Dunjic Manevski Sofija , Radojkovic Dragica , Golic Natasa
Published: May 2022

Bronchial epithelial cells are exposed to environmental influences, microbiota, and pathogens and also serve as a powerful effector that initiate and propagate inflammation by the release of pro-inflammatory mediators. Recent studies suggested that lung microbiota differ between inflammatory lung diseases and healthy lungs implicating their contribution in the modulation of lung immunity. Lactic acid bacteria (LAB) are natural inhabitants of healthy human lungs and also possess immunomodulatory effects, but so far, there are no studies investigating their anti-inflammatory potential in respiratory cells. In this study, we investigated immunomodulatory features of 21 natural LAB strains in lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Our results show that several LAB strains reduced the expression of pro-inflammatory cytokine and chemokine genes. We also demonstrated that two LAB strains, Lactobacillus brevis BGZLS10-17 and Lb. plantarum BGPKM22, effectively attenuated LPS-induced nuclear factor-κB (NF-κB) nuclear translocation. Moreover, BGZLS10-17 and BGPKM22 reduced the activation of p38, extracellular signal-related kinase (ERK), and c-Jun amino-terminal kinase (JNK) signaling cascade resulting in a reduction of pro-inflammatory mediator expressions in BEAS-2B cells. Collectively, the LAB strains BGZLS10-17 and BGPKM22 exhibited anti-inflammatory effects in BEAS-2B cells and could be employed to balance immune response in lungs and replenish diminished lung microbiota in chronic lung diseases.
ASC-J9 Blocks Cell Proliferation and Extracellular Matrix Production of Keloid Fibroblasts through Inhibiting STAT3 Signaling
Authors: Hong Yi-Kai , Wu Chen-Han , Lin Yu-Chen , Huang Yu-Lun , Hung Kuo-Shu , Pai Tsung-Pin , Liu Yen-Ting , Chen Tzu-Chi , Chan Hardy , Hsu Chao-Kai
Published: May 2022

Keloids are a fibrotic skin disorder caused by abnormal wound healing and featuring the activation and expansion of fibroblasts beyond the original wound margin. Signal transducer and activator of transcription 3 (STAT3) has been found to mediate the biological functions of keloid fibroblasts (KFs). Therefore, we aimed to demonstrate whether ASC-J9, an inhibitor of STAT3 phosphorylation, can suppress the activation of KFs. Western blotting results showed that ASC-J9 inhibited the levels of COL1A1 and FN1 proteins, which were upregulated in KFs, by decreasing the expression of pSTAT3 and STAT3. RNA sequencing and in vitro studies further demonstrated that ASC-J9 treatment of KFs reduced cell division, inflammation, and ROS generation, as well as extracellular matrix (ECM) synthesis. ELISA assays verified that ASC-J9 treatment significantly mitigated IL-6 protein secretion in KFs. Transmission electron microscopy images revealed that ASC-J9 induced the formation of multilamellar bodies in KFs, which is associated with autophagy-related signaling. These results suggested that inhibiting a vicious cycle of the ROS/STAT3/IL-6 axis by ASC-J9 may represent a potential therapeutic approach to suppress cell proliferation and ECM production in KFs.
Mitochondrial Bioenergetics in Different Pathophysiological Conditions 2.0
Authors: Valenti Daniela , Atlante Anna
Published: May 2022

Mitochondria, traditionally identified as the powerhouses of eukaryotic cells, constitute a dynamic network of signaling platforms with multifaceted key roles in cell metabolism, proliferation and survival [...]
β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression
Authors: Sun Wenjuan , Kim Dong Hyun , Byon Chang Hyun , Choi Hoon In , Park Jung Sun , Bae Eun Hui , Ma Seong Kwon , Kim Soo Wan
Published: May 2022

Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and β-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of β-elemene was demonstrated by in vivo and in vitro experiments. It was shown that β-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-β stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that β-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-β stimulated NRK49F cell, which may be a novel molecular mechanism by which β-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of β-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.
Adsorption of Biomineralization Protein Mms6 on Magnetite (Fe3O4) Nanoparticles
Authors: Arai Kosuke , Murata Satoshi , Wang Taifeng , Yoshimura Wataru , Oda-Tokuhisa Mayumi , Matsunaga Tadashi , Kisailus David , Arakaki Atsushi
Published: May 2022

Biomineralization is an elaborate process that controls the deposition of inorganic materials in living organisms with the aid of associated proteins. Magnetotactic bacteria mineralize magnetite (Fe3O4) nanoparticles with finely tuned morphologies in their cells. Mms6, a magnetosome membrane specific (Mms) protein isolated from the surfaces of bacterial magnetite nanoparticles, plays an important role in regulating the magnetite crystal morphology. Although the binding ability of Mms6 to magnetite nanoparticles has been speculated, the interactions between Mms6 and magnetite crystals have not been elucidated thus far. Here, we show a direct adsorption ability of Mms6 on magnetite nanoparticles in vitro. An adsorption isotherm indicates that Mms6 has a high adsorption affinity (Kd = 9.52 µM) to magnetite nanoparticles. In addition, Mms6 also demonstrated adsorption on other inorganic nanoparticles such as titanium oxide, zinc oxide, and hydroxyapatite. Therefore, Mms6 can potentially be utilized for the bioconjugation of functional proteins to inorganic material surfaces to modulate inorganic nanoparticles for biomedical and medicinal applications.
Involvement of ORAI1/SOCE in Human AML Cell Lines and Primary Cells According to ABCB1 Activity, LSC Compartment and Potential Resistance to Ara-C Exposure
Authors: Lewuillon Clara , Guillemette Aurélie , Titah Sofia , Shaik Faruk , Jouy Nathalie , Labiad Ossama , Farfariello Valerio , Laguillaumie Marie-Océane , Idziorek Thierry , Barthélémy Adeline , Peyrouze Pauline , Berthon Céline , Tarhan Mehmet , Cheok Meyling , Quesnel Bruno , Lemonnier Loïc , Touil Yasmine
Published: May 2022

Acute myeloid leukemia (AML) is a hematological malignancy with a high risk of relapse. This issue is associated with the development of mechanisms leading to drug resistance that are not yet fully understood. In this context, we previously showed the clinical significance of the ATP binding cassette subfamily B-member 1 (ABCB1) in AML patients, namely its association with stemness markers and an overall worth prognosis. Calcium signaling dysregulations affect numerous cellular functions and are associated with the development of the hallmarks of cancer. However, in AML, calcium-dependent signaling pathways remain poorly investigated. With this study, we show the involvement of the ORAI1 calcium channel in store-operated calcium entry (SOCE), the main calcium entry pathway in non-excitable cells, in two representative human AML cell lines (KG1 and U937) and in primary cells isolated from patients. Moreover, our data suggest that in these models, SOCE varies according to the differentiation status, ABCB1 activity level and leukemic stem cell (LSC) proportion. Finally, we present evidence that ORAI1 expression and SOCE amplitude are modulated during the establishment of an apoptosis resistance phenotype elicited by the chemotherapeutic drug Ara-C. Our results therefore suggest ORAI1/SOCE as potential markers of AML progression and drug resistance apparition.
AG1478 Elicits a Novel Anti-Influenza Function via an EGFR-Independent, GBF1-Dependent Pathway
Authors: Zhou Xu , Zhu Lingxiang , Bondy Cheryl , Wang Jun , Luo Qianwen , Chen Yin
Published: May 2022

Current options for preventing or treating influenza are still limited, and new treatments for influenza viral infection are urgently needed. In the present study, we serendipitously found that a small-molecule inhibitor (AG1478), previously used for epidermal growth factor receptor (EGFR) inhibition, demonstrated a potent activity against influenza both in vitro and in vivo. Surprisingly, the antiviral effect of AG1478 was not mediated by its EGFR inhibitory activity, as influenza virus was insensitive to EGFR blockade by other EGFR inhibitors or by siRNA knockdown of EGFR. Its antiviral activity was also interferon independent as demonstrated by a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout approach. Instead, AG1478 was found to target the Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1)–ADP-ribosylation factor 1 (ARF1) system by reversibly inhibiting GBF1 activity and disrupting its Golgi-cytoplasmic trafficking. Compared to known GBF1 inhibitors, AG1478 demonstrated lower cellular toxicity and better preservation of Golgi structure. Furthermore, GBF1 was found to interact with a specific set of viral proteins including M1, NP, and PA. Additionally, the alternation of GBF1 distribution induced by AG1478 treatment disrupted these interactions. Because targeting host factors, instead of the viral component, imposes a higher barrier for developing resistance, GBF1 modulation may be an effective approach to treat influenza infection.
Glycosylation of Methylflavonoids in the Cultures of Entomopathogenic Filamentous Fungi as a Tool for Obtaining New Biologically Active Compounds
Authors: Krawczyk-Łebek Agnieszka , Dymarska Monika , Janeczko Tomasz , Kostrzewa-Susłow Edyta
Published: May 2022

Flavonoid compounds are secondary plant metabolites with numerous biological activities; they naturally occur mainly in the form of glycosides. The glucosyl moiety attached to the flavonoid core makes them more stable and water-soluble. The methyl derivatives of flavonoids also show increased stability and intestinal absorption. Our study showed that such flavonoids can be obtained by combined chemical and biotechnological methods with entomopathogenic filamentous fungi as glycosylation biocatalysts. In the current paper, two flavonoids, i.e., 2′-hydroxy-4-methylchalcone and 4′-methylflavone, have been synthesized and biotransformed in the cultures of two strains of entomopathogenic filamentous fungi Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5. Biotransformation of 2′-hydroxy-4-methylchalcone resulted in the formation of two dihydrochalcone glucopyranoside derivatives in the culture of I. fumosorosea KCH J2 and chalcone glucopyranoside derivative in the case of B. bassiana KCH J1.5. 4′-Methylflavone was transformed in the culture of I. fumosorosea KCH J2 into four products, i.e., 4′-hydroxymethylflavone, flavone 4′-methylene-O-β-d-(4″-O-methyl)-glucopyranoside, flavone 4′-carboxylic acid, and 4′-methylflavone 3-O-β-d-(4″-O-methyl)-glucopyranoside. 4′-Methylflavone was not efficiently biotransformed in the culture of B. bassiana KCH J1.5. The computer-aided simulations based on the chemical structures of the obtained compounds showed their improved physicochemical properties and antimicrobial, anticarcinogenic, hepatoprotective, and cardioprotective potential.