bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparities in Prevalence and Barriers to Hypertension Control: A Systematic Review
Authors: Elnaem Mohamed Hassan , Mosaad Manar , Abdelaziz Doaa H , Mansour Noha O. , Usman Abubakar , Elrggal Mahmoud E. , Cheema Ejaz
Published: November 2022

Controlling hypertension (HTN) remains a challenge, as it is affected by various factors in different settings. This study aimed to describe the disparities in the prevalence and barriers to hypertension control across countries of various income categories. Three scholarly databases—ScienceDirect, PubMed, and Google Scholar—were systematically examined using predefined search terms to identify potentially relevant studies. Original research articles published in English between 2011 and 2022 that reported the prevalence and barriers to HTN control were included. A total of 33 studies were included in this systematic review. Twenty-three studies were conducted in low and middle-income countries (LMIC), and ten studies were from high-income countries (HIC). The prevalence of hypertension control in the LMIC and HIC studies ranged from (3.8% to 50.4%) to (36.3% to 69.6%), respectively. Concerning barriers to hypertension control, patient-related barriers were the most frequently reported (n = 20), followed by medication adherence barriers (n = 10), lifestyle-related barriers (n = 8), barriers related to the affordability and accessibility of care (n = 8), awareness-related barriers (n = 7), and, finally, barriers related to prescribed pharmacotherapy (n = 6). A combination of more than one category of barriers was frequently encountered, with 59 barriers reported overall across the 33 studies. This work reported disparities in hypertension control and barriers across studies conducted in LMIC and HIC. Recognizing the multifactorial nature of the barriers to hypertension control, particularly in LMIC, is crucial in designing and implementing customized interventions.
Transformation Path of Ecological Product Value and Efficiency Evaluation: The Case of the Qilihai Wetland in Tianjin
Authors: Yu Hang , Shao Chaofeng , Wang Xiaojun , Hao Chunxu
Published: November 2022

In order to protect wetland resources, China has developed wetland conservation policies and has made significant conservation investments, but there is still a lack of pathways for the conversion to economic value, making it difficult to meet the demand for continuous investment. We have explored a sustainable ecological conservation mechanism using the Seven Mile Sea as a case study, so that ecological conservation costs can be transformed into economic development behaviors and ecological benefits and socio-economic development can be integrated. This paper assesses the ecological product value of the Qilihai Wetland based on the ecosystem service function value assessment method, which designs the realization path of ecological product value and predicts the value transformation efficiency. The results show the following: (1) The total value of ecological products in the study area is CNY 569.06 million (USD 78.36 million), and the main sources of value are plant products in the supply service and water purification functions in the regulation service, accounting for 54.05% and 26.10% of the total, respectively. (2) The predicted value realization of ecological products, ideally, is CNY 689.65 million (USD 94.96 million), with a value realization rate of 111.60%. Considering the management policy restrictions in different areas of the Qilihai Wetland, the actual value realization volume is CNY 391.94 million (USD 53.97 million), with a value realization rate of 63.42%. (3) Owing to the restriction of the development policy of supply services and cultural services, the value realization path mainly contains two types: one is to drive the development of supply services and cultural services in the surrounding areas, along with product premiums, to realize value transformation. This path is mainly aimed at the supply of local characteristic products and the development of tourism. The second is to realize the value of regulating services through ecological compensation and ecological equity trading. This path is mainly for the adjustment and support services in the core area and buffer area. According to the pre-accounting results, the contribution rates of the two paths are 62.25% and 37.75%, respectively. The second path should be further effectively developed to improve the contribution rate. This study helps assess the ecological value and important ecological elements of the Qilihai Wetland to ensure effective protection and development of important ecological resources and to achieve the sustainable development of wetland resources. It provides a reference for exploring feasible paths to realize the value of ecological goods.
Shrinking Working-Age Population and Food Demand: Evidence from Rural China
Authors: Han Xinru , Xue Ping , Zhu Wenbo , Wang Xiudong , Li Guojing
Published: November 2022

China is facing a rapidly aging population, and the proportion of the working-age population (WAP) is showing a decreasing trend. In this study, we use a two-stage budgeting quadratic almost-ideal demand system framework to estimate the distribution of food demand elasticity under different proportions of the WAP in rural China. The results show that the income elasticities of rural residents’ demand for fruits and vegetables, animal products, oils and fats, and grains were 0.73, 0.65, 0.55, and 0.48, respectively. Additionally, the income elasticity of rural residents tended to increase as the household proportion of the WAP decreased. These results can provide a deeper understanding of the food consumption patterns of rural residents in China, and could be used in general or partial equilibrium models to forecast food supply and demand.
Exposure to Nature Sounds through a Mobile Application in Daily Life: Effects on Learning Performance among University Students
Authors: Luo Jiutong , Wang Minhong , Chen Boyin , Sun Meng
Published: November 2022

Previous studies have revealed the restorative effects of exposure to natural environments on psychological well-being and cognitive performance. Recent studies have reported the effects of exposure to nature sounds (e.g., the sounds of birds, rainfall, and waves) through a mobile application on reducing students’ mental fatigue and improving their cognitive performance. However, it remains unknown whether exposure to nature sounds through a mobile application may influence students’ learning performance. To address the gap, we conducted a study with 71 university students. During the four-week intervention, 36 students in the experimental group were exposed to nature sounds through a free mobile application for at least 30 consecutive minutes per day when working on academic-related tasks; 35 students in the control group did not have such exposure when working on similar tasks. The results show that students in the experimental group outperformed those in the control group in their engagement in deep learning, frequency of academic procrastination, and academic self-efficacy. The findings reveal the promising effects of exposure to nature sounds through a mobile application on improving students’ learning performance. The implications of the findings are discussed.
The Effects of Paroxetine on Benthic Microbial Food Web and Nitrogen Transformation in River Sediments
Authors: Li Yi , Chen Xinqi , Wang Xinzi , Shang Jiahui , Niu Lihua , Wang Longfei , Zhang Huanjun , Zhang Wenlong
Published: November 2022

Paroxetine is a common pharmaceutical to treat depression and has been found to pose threats to aquatic organisms. However, little is known about the effects of paroxetine on the nutrient cycle in aquatic environments. Therefore, DNA metabarcoding is used in this study to analyze the effects of paroxetine on multi-trophic microorganisms and nitrogen transformation in river sediments. Although paroxetine has no significant effect on the diversity of microbenthos, changes in benthic nitrogen-converting bacteria are consistent with the change in the various forms of nitrogen in the sediment, indicating that paroxetine affects the nitrogen conversion process by affecting nitrogen-converting bacteria. In addition, it is found that paroxetine has the ability to influence nitrogen transformation in an indirect way by affecting the trophic transfer efficiency of higher trophic levels (meiofauna and protozoa, protozoa and protozoa), subsequently affecting the growth of nitrogen-converting bacteria through a top-down mechanism (i.e., predation).The results show that paroxetine affects nitrogen transformation directly by affecting nitrogen-converting bacteria and indirectly through top-down effects, emphasizing that the assessment of paroxetine’s ecological risks should consider species within different trophic levels.
Trade and Embodied CO2 Emissions: Analysis from a Global Input–Output Perspective
Authors: Zhou Xinsheng , Guo Qinyang , Wang Yuanyuan , Wang Guofeng
Published: November 2022

Global trade drives the world’s economic development, while a large amount of embodied carbon is transferred among different countries and regions. Based on a multi-regional input–output model, the trade embodied carbon transfers of bilateral trade between 185 countries/regions around the world were calculated. On the basis, regional trade embodied carbon transfer patterns and major national trade patterns in six continents, eight major economic cooperation organizations, and six representative countries/regions were further analyzed. The results showed that Europe was the continent with the largest embodied carbon inflows from trade and Africa was the continent with the largest embodied carbon outflows from trade. China was the country which had the largest embodied carbon outflows from trade, while the United States, France, Japan, and Germany were countries which had embodied carbon inflows from trade. OECD, EU, and NAFTA were the economic cooperation organizations with embodied carbon inflows from trade, while BRICS, SCO, RCEP, OPEC, and ASEAN were economic cooperation organizations with embodied carbon outflows from trade. Developed countries such as the United States, France, and the United Kingdom protected their environment by exporting high-value products and importing low-value and carbon-intensive products. Developing countries such as China and Russia earned foreign exchange by exporting carbon-intensive and commodity products at a huge environmental cost. In contrast, Germany, China, and Russia played different roles in the global industrial chain, while Germany exchanged more trade surpluses at lower environmental costs. Therefore, for different countries and regions, their own industries should be actively upgraded to adjust the import and export structure, the cooperation and coordination in all regions of the world should be strengthened, and the transfers of embodied carbon needs to be reduced to make the trade model sustainable.
Effects of Service Quality Characteristics of Neighborhood Sports Facilities on User Satisfaction and Reuse Intention of the Elderly during the COVID-19 Pandemic
Authors: Cho Kyoung Hwan , Park Jeong-Beom , Jung Yang Hun
Published: November 2022

Purpose: this study aimed to examine the user satisfaction and reuse intention of the elderly for neighborhood sports facilities in South Korea during the COVID-19 pandemic. Methods: this study surveyed 386 Korean elderly individuals aged ≥ 65 years, who were users of neighborhood sports facilities, from 1 May to 31 August 2022. A total of 386 questionnaires were used for data analysis, which was carried out using SPSS 23.0 statistical software. Descriptive statistics of the mean, standard deviation, and frequency distribution were used at the descriptive level. Moreover, one-way analysis of variance (ANOVA), Scheffe’s post hoc pair-wise comparison analysis, Pearson’s correlation coefficient, and multiple regression analysis were used at the inferential level. The significance level of these tests was considered for less than 0.05. Results: the mechanistic and humanistic service factors of neighborhood sports facilities affected user satisfaction and reuse intention. Furthermore, user satisfaction of the elderly during the COVID-19 pandemic had a positive effect on reuse intention. Conclusion: this study confirmed that the service quality characteristics of neighborhood sports facilities during the COVID-19 pandemic had a positive effect on user satisfaction and intention to continue to exercise among the elderly.
Recent Advance Analysis of Recovery in Hospitalized People with COVID-19: A Systematic Review
Authors: Santos Joyce Noelly Vitor , Mendonça Vanessa Amaral , Fernandes Amanda Cristina , Maia Laísa Braga , Henschke Nicholas , de Souza Mateus Bastos , da Silva Lage Vanessa Kelly , Oliveira Murilo Xavier , de Fátima Silva Angélica , Rodrigues Lacerda Ana Cristina , Sartorio Alessandro , Rapin Amandine , de Oliveira Vinícius Cunha , Taiar Redha
Published: November 2022

Introduction: COVID-19 is a public health emergency all around the world. Severe illness occurred in about 14% of patients and 5% of patients developed critical illness, but the prognosis for these patients remains unclear. Objective: To describe the prognosis in hospitalized adults with COVID-19. Methods: The MEDLINE, EMBASE, AMED, and COCHRANE databases were searched for studies published up to 28 June 2021 without language restrictions. Descriptors were related to “COVID-19” and “prognosis”. Prospective inception cohort studies that assessed morbidity, mortality and recovery in hospitalized people over 18 years old with COVID-19 were included. Two independent reviewers selected eligible studies and extracted the available data. Acute respiratory distress syndrome (ARDS) and multiple organ failure (MOFS) were considered as outcomes for morbidity and discharge was considered for recovery. The Quality in Prognosis Studies (QUIPS) tool was used to assess risk of bias. Analyses were performed using Comprehensive Meta-Analysis (version 2.2.064). Results: We included 30 inception cohort studies investigating 13,717 people hospitalized with COVID-19 from different countries. The mean (SD) age was 60.90 (21.87) years, and there was high proportion of males (76.19%) and people with comorbidities (e.g., 49.44% with hypertension and 29.75% with diabetes). Findings suggested a high occurrence of morbidity, mainly related to ARDS. Morbidity rates varied across studies from 19% to 36% in hospital wards, and from 13% to 90% in Intensive Care Units—ICU. Mortality rates ranged from 4% to 38% in hospital wards and from 8% to 51% in ICU. Recovery rates ranged up to 94% and 65% in hospital wards and ICU, respectively. The included studies had high risk of bias in the confounding domain. Conclusions: The prognosis of people hospitalized with COVID-19 is an issue for the public health system worldwide, with high morbidity and mortality rates, mainly in ICU and for patients with comorbidities. Its prognosis emphasizes the need for appropriate prevention and management strategies.
The Effect of Cognitive Strategies and Facial Attractiveness on Empathic Neural Responses
Authors: Balconi Michela , Kopiś-Posiej Natalia , Venturella Irene , Zabielska-Mendyk Emilia , Augustynowicz Paweł , Angioletti Laura
Published: November 2022

Empathy is a phenomenon that brings together both emotions and an understanding of another person. Recent studies have disentangled the mechanisms of empathy into emotional and cognitive aspects. Event-related potential (ERP) studies suggest that emotional empathy is related to the modulation of the amplitude of early ERPs, and cognitive empathy is linked to later ERPs. In the current study, we examined the influences of facial attractiveness on empathic response and the effect of cognitive strategies with setting the participants’ attention to attractiveness or pain. Participants (N= 19) viewed photos of physically attractive and unattractive men and women receiving painful stimulation. The amplitude of the N2 component measured at the frontal regions was more negative in painful stimulation compared to the non-painful, but only for attractive faces. There were no differences between painful and non-painful stimulation for unattractive faces. The amplitude of the P3 measured at the central-parietal region component was more positive in the painful condition compared to the non-painful one, but only when participants performed a pain judgment task. There were no differences in the attractiveness judgment task. This study showed that the attractiveness of a model and drawing the participants’ attention to pain constitute an essential modulator of pain empathy.
Assessing Quality of Life with Community Dwelling Elderly Adults: A Mass Survey in Taiwan
Authors: Chi Ying-Chen , Wu Chen-Long , Liu Hsiang-Te
Published: November 2022

Background: With the growing life expectancy for older adults, this study aims to examine the correlation among sociodemographic characteristics and the combined effect of QoL-related domains including physical health, psychological health, social relationships, and environmental factors with the overall QoL level of older adults in Taiwan. Methods: The WHOQOL-BREF Taiwanese Version questionnaire was adopted and conducted using a randomized telephone interview system from community household elders. In total, 1078 participants aged 65 years and older were recruited. A multiple regression model was used to examine the statistical significance between the overall QoL score as the dependent variable and the sociodemographic characteristics, and 26 items of QoL-related questionnaires as the independent variables. Results: Categories including female, aged 85 years and above, higher education level, and better financial situation had significantly higher overall QoL level. Except the physical health domain and six items, the correlations among all other domains and their including items of questionnaires with overall QoL level were significant. Conclusion: The Taiwanese WHOQOL-BREF questionnaire can be used to examine the overall QoL level of elders in Taiwan. Nevertheless, the robust systems of universal health care and long-term care in Taiwan may have led to the no significance of the six items.
Voting with Your Feet: The Impact of Urban Public Health Service Accessibility on the Permanent Migration Intentions of Rural Migrants in China
Authors: Zhao Qingjun , Song Meijing , Wang Hanrui
Published: November 2022

The accessibility of urban public health services is not only relevant to the health status of rural migrants but also plays an increasingly important role in their migration decisions. Most existing studies have focused on the effects of the level of public health service provision and parity on rural migrants’ migration behavior, ignoring the role of public health service accessibility. This paper systematically examines the overall impact, heterogeneous impact and mechanism of action of public health service accessibility on rural migrants’ intentions to migrate permanently based on data from the 2017 China Mobile Population Dynamics Monitoring Survey using probit, IVprobit, eprobit, omitted variable test model and KHB mediating effect model. It was found that: (1) public health service accessibility significantly increased rural migrants’ intentions to migrate permanently, and the results remained robust after using instrumental variables to mitigate endogeneity problems and omitted variable tests. (2) Heterogeneity analysis shows that public health service accessibility has a greater effect on enhancing the intentions to migrate permanently among females and rural migrants born in 1980 and later. (3) Further mechanism testing revealed that public health service accessibility could indirectly increase rural migrants’ intentions to migrate permanently by improving health habits, health status, identity, and social integration, with identity playing a greater indirect effect. The findings of this paper not only provide empirical evidence for the existence of Tiebout’s “voting with your feet” mechanism in China but also contribute to the scientific understanding of the role of equalization of public health services in the process of population migration.
Walking Behavior of Older Adults in Temuco, Chile: The Contribution of the Built Environment and Socio-Demographic Factors
Authors: Paydar Mohammad , Kamani Fard Asal
Published: November 2022

The amount of walking for daily transport has decreased significantly over the last decades in Temuco, Chile. Moreover, the percentage of older adults (aged over 65) who did not meet the recommendations of at least 150 min of physical activity per week has increased during this time. In this regard, the present study examines the contribution of socio-demographic and built environment factors on the walking behavior of older adults in Temuco, Chile, with a view to improving their level of physical activity. A cross-sectional study was conducted among 463 older adults aged 60 years and over. Travel Diary Data taken from “Encuesta Origin Destino” (EOD) 2013, Geographic information systems (GIS), audits (PEDS with certain revisions) and finally, multiple regression analysis, were used to examine the objectives. Associations were found between the walking behavior of older adults and several socio-demographic factors, as well as several built environment factors including destination (the number of parks and the land use mix), functionality (street connectivity, length of street sections and off-street parking lots) and aesthetics (views of nature, building height, and articulation in building design). These findings should be considered by urban/transport policymakers to improve the walking behavior of older adults in this city.
Discrepancy between Food Classification Systems: Evaluation of Nutri-Score, NOVA Classification and Chilean Front-of-Package Food Warning Labels
Authors: Valenzuela Aranza , Zambrano Leandro , Velásquez Rocío , Groff Catalina , Apablaza Tania , Riffo Cecilia , Moldenhauer Sandra , Brisso Pamela , Leonario-Rodriguez Marcell
Published: November 2022

Background: Currently, there are different food classification systems in order to inform the population of the best alternatives for consumption, considering all the diseases associated with the consumption of products of low nutritional quality. Reports indicate that these forms of labelling warnings correspond to a laudable strategy for populations that do not have the knowledge to discriminate between the wide range of products offered by the food industry. However, recent publications indicate that there may be inconsistencies between the different classification guidelines, and the guidelines that nations should adopt in their food guides are still a matter of debate. In view of this, the present study aimed to evaluate the quantitative and qualitative differences that exist between the NOVA, Nutri-Score and Chilean Front-of-package (FoP) food warning label according to the Chilean basic food basket list. Method: An analytical study was carried out to classify a list of 736 foods according to three different systems, evaluating the distributions according to their methods of classifying the products. Quantitative differences were contrasted for each system, as well as between them, together with an analysis of the dimensions of each system. Results: According to the Nutri-Score classification, the most frequent category was A with 27% (high nutritional quality), followed by D with 22% (low nutritional quality) of the total. On the other hand, the NOVA classification showed that the most frequent categorization was ultra-processed food (NOVA 4) with 54%, followed by unprocessed (NOVA 1) with 19%. Regarding the FoP warning labels, 57% of the foods were categorized as free warning labels, followed by the category of foods with 3 warning labels (23%). Regarding the results of the principal component analysis, the Nutri-Score and FoP warning labels present a degree of similarity in their classification guidelines, being different than the dimension pointed out by NOVA. Conclusion: The present work managed to demonstrate that there are quantitative and qualitative differences between the classification and recommendation guidelines of the Nutri-Score, NOVA and FoP warning labels, finding concrete discrepancies between them.
Effects of Recreational Physical Activity on Abdominal Obesity in Obese South Korean Adults
Authors: Lee Yoonmi , Kwak Sungjung , Shin Jieun
Published: November 2022

This study investigated the effects of general characteristics, health behaviors, and level of physical activity on abdominal obesity in obese adults (BMI (body mass index) ≥ 25 kg/m2) using data from the seventh period (2016–2018) of the Korea National Health and Nutrition Examination Survey (KNHANES). We also prepared basic data on the improvement and management of abdominal obesity. The participants were 2343 obese adults (men, 1338; women, 1005) from the KNHANES. Factors relevant to abdominal obesity in obese Korean women were general characteristics (age, marital status, occupation, education, and menopause) and health behaviors (time for recreational physical activities and energy intake). In men, these factors tended to be health behaviors, including time spent on leisure physical activity, and sitting. It was found that over 600 Mets/week of recreational physical activity for both adult men and women reduced the incidence of abdominal obesity after adjusting for general characteristics and health behaviors (odds ratio (95% CI); men 0.69 (0.51–0.92); women, 0.61 (0.40–0.94)). Therefore, to prevent or improve abdominal obesity in obese adults in Korea, it is necessary to consider general characteristics and health behaviors according to sex. In addition, maintaining a physical activity rate of over 600 Mets/week is also recommended.
Adult Worker Model Typologies: Examining Work–Family Policies in Fifteen European Countries
Authors: Lo Iris Po Yee , Chau Ruby Chui Man , Yu Sam Wai Kam
Published: November 2022

This article aims to advance the discussion of government policies for improving women’s work and family life. It focuses on exploring whether it is reasonable to expect that the supported adult worker model will play an important role in guiding governments to reduce the gender employment gap and, at the same time, increase women’s resources for strengthening their control over family and work life. This model posits that governments should take a proactive approach to encouraging women to take part in formal employment, such as providing care support measures. To examine the impact of the model, this article develops an ‘input adult worker model typology’ and an ‘output adult worker model typology’ using cluster analysis of comparative data covering 15 countries. The findings show that it is important not to overestimate the impact of the supported adult worker model on reducing the gender employment gap or increasing women’s control over their lives in most of the 15 countries. The evidence generated from these typologies highlights the difficulties involved in promoting women’s welfare despite the use of the adult worker model as a substitute for the male-breadwinner model.
Climate Change Prevention through Community Actions and Empowerment: A Scoping Review
Authors: Salvador Costa Maria , Leitão Alexandra , Silva Rosa , Monteiro Vanessa , Melo Pedro
Published: November 2022

As society tries to tackle climate change around the globe, communities need to reduce its impact on human health. The purpose of this review is to identify key stakeholders involved in mitigating and adapting to climate change, as well as the type and characteristics of community empowerment actions implemented so far to address the problem. Published and unpublished studies from January 2005 to March 2022 in English and Portuguese were included in this review. The search, conducted on PubMed, CINAHL, Scopus, MEDLINE, Scopus, Web of Science, SciELO, and RCAAP (Repositório Científico de Acesso Aberto de Portugal), followed a three-step search strategy. Data extraction was performed by two independent reviewers, using an extraction tool specifically designed for the review questions. Twenty-seven studies were eligible for inclusion: six used interviews as a qualitative method, three were systematic reviews, three were case study analyses, three used surveys and questionnaires as quantitative methods, two used integrative baseline reviews, and three utilized a process model design. Six studies targeted local, public and private stakeholders. Community settings were the context target of fifteen studies, whereas twelve specifically referred to urban settings. Seven types of community actions were acknowledged across the globe, characterised as hybrid interventions and referring to the leading stakeholders: local governments, non-governmental organizations, civil society, universities, public health, and private sectors.
An Analysis of Factors Shaping Vaccine Attitudes and Behaviours in a Low-Trust Society Based on Structural Equation Modelling—The Case of Poland’s Vaccination Programme against COVID-19
Authors: Wróblewski Michał , Meler Andrzej , Stankowska Joanna , Kawiak-Jawor Ewa
Published: November 2022

This study focuses on factors that shape vaccine attitudes and behaviours in the context of a low-trust society. Our analysis focuses on the Polish vaccination programme against COVID-19, primarily on (1) the evaluation of the information campaign, (2) trust in the institutions, (3) trust in other people, (4) attitudes toward vaccine safety and efficacy, (5) attitudes toward restrictions related to vaccination (e.g., restricted access to certain services for unvaccinated persons) and the introduction of mandatory vaccination, (6) the evaluation of the government’s actions during the pandemic, and (7) political preferences. The study was conducted with a sample of 1143 adult residents in Poland (CATI). The explanation of the factors determining the COVID-19 vaccine was based on structural equation modelling (SEM). The model showed that the declared fact of vaccination was largely determined by a positive attitude toward restrictions related to vaccination and trust in vaccines. The formation of the provaccine attitude was to an extent determined by the assessment of the government’s campaign and actions during pandemic. While institutional trust had a positive effect on support for the ruling coalition (0.56), the latter on its own had the opposite effect (−0.61) on the formation of provaccine attitude. In the group who both trust institutions and support the parties currently in power, there are more of those who simultaneously reject the restrictions and mandatory vaccination and remain sceptical about the safety and efficacy of COVID-19 vaccines than those who both trust in the vaccine safety and efficacy and accept the restrictions and mandatory vaccination. This indicates that in the context of strong political polarisation, ideological affiliations may play a greater role in shaping vaccine attitudes and behaviours than institutional trust.
New Molecules of Diterpene Origin with Inhibitory Properties toward α-Glucosidase
Authors: Tretyakova Elena , Smirnova Irina , Kazakova Oxana , Nguyen Ha Thi Thu , Shevchenko Alina , Sokolova Elena , Babkov Denis , Spasov Alexander
Published: November 2022

The incidence of diabetes mellitus (DM), one of the most common chronic metabolic disorders, has increased dramatically over the past decade and has resulted in higher rates of morbidity and mortality worldwide. The enzyme, α-Glucosidase (α-GLy), is considered a therapeutic target for the treatment of type 2 DM. Herein, we synthesized arylidene, heterocyclic, cyanoetoxy- and propargylated derivatives of quinopimaric acid (levopimaric acid diene adduct with p-benzoquinone) 1–50 and, first, evaluated their ability to inhibit α-GLy. Among the tested compounds, quinopimaric acid 1, 2,3-dihydroquinopimaric acid 8 and its amide and heterocyclic derivatives 9, 30, 33, 39, 44, with IC50 values of 35.57–65.98 μM, emerged as being good inhibitors of α-GLy. Arylidene 1β-hydroxy and 1β,13α-epoxy methyl dihydroquinopimarate derivatives 6, 7, 26–29, thiadiazole 32, 1a,4a-dehydroquinopimaric acid 40 and its indole, nitrile and propargyl hybrids 35–38, 42, 45, 48, and 50 showed excellent inhibitory activities. The most active compounds 38, 45, 48, and 50 displayed IC50 values of 0.15 to 0.68 μM, being 1206 to 266 more active than acarbose (IC50 of 181.02 μM). Kinetic analysis revealed the most active diterpene indole with an alkyne substituent 45 as a competitive inhibitor with Ki of 50.45 μM. Molecular modeling supported this finding and suggested that the indole core plays a key role in the binding. Compound 45 also has favorable pharmacokinetic and safety properties, according to the computational ADMET profiling. The results suggested that quinopimaric acid derivatives should be considered as potential candidates for novel alternative therapies in the treatment of type 2 diabetes.
An Amide Alkaloid Isolated from Ephedra sinica Ameliorates OVA-Induced Allergic Asthma by Inhibiting Mast Cell Activation and Dendritic Cell Maturation
Authors: Jia Jufang , Zeng Mengnan , Zhu Denghui , Jiao Xinmian , Zhang Beibei , Yang Ruolan , Feng Weisheng , Zheng Xiaoke
Published: November 2022

Asthma, which is a chronic inflammatory disease of the airways, is usually caused by allergens in which various structures and immune cells are involved. Ephedra sinica, the most commonly used Chinese medicine, has significant clinical effects on asthma, but its components are complex and the mechanism of action has not been fully elucidated. Among its components, we identified an amide alkaloid (EB-A) and investigated its anti-asthmatic activity and the underlying mechanisms. In this study, we replicated an OVA-sensitized/challenged allergic asthma mouse model, and divided the mice into a model (OVA) group, positive drug (Y, 0.5 mg/kg/day) group, and EB-A treatment with low (Low, 10 mg/kg/day) and high dose (High, 20 mg/kg/day) groups. Asthma-related features were analyzed through the airway hyperresponsiveness (AHR), cough and wheeze indexes, allergen-specific IgE, prostaglandin D2 (PDG2), and lung histology in mice. The levels of apoptosis and reactive oxygen species (ROS) in the primary lung cells, cytokines in the serum and broncho-alveolar lavage fluid (BALF), and proteinase-activated receptor-2 (PAR2) pathway activation in the lung tissue were measured to evaluate the inflammatory injury and lung epithelial barrier damage in the mice. Dendritic cell (DC) maturation and mast cell (MC) activation were verified in vitro and in vivo. Furthermore, the effect of a PAR2 activation in lung epithelial cells on the maturation of DCs was evaluated by the co-culture system of (human bronchial epithelial cell lines) 16HBE and bone marrow-derived dendritic cells (BMDCs). The results showed that EB-A inhibited the typical asthmatic phenotypes, as well as lung injury and inflammation, MC activation and degranulation, and DC maturation in the OVA-sensitized/challenged BALB/c mice. In addition, EB-A inhibited the expression of PAR2 in the lung epithelial cells and significantly interfered with the maturation of DCs after inhibiting PAR2. Taken together, our study firstly demonstrated that EB-A could ameliorate OVA-induced allergic asthma by inhibiting MC activation and DC maturation, and the molecular mechanism of EB-A’s anti-asthmatic activity might be mediated by inhibiting PAR2. Our data provide a molecular justification for the use of EB-A in the treatment of allergic asthma.
Insect Gut Bacteria Promoting the Growth of Tomato Plants (Solanum lycopersicum L.)
Authors: Krawczyk Krzysztof , Szabelska-Beręsewicz Alicja , Przemieniecki Sebastian Wojciech , Szymańczyk Mateusz , Obrępalska-Stęplowska Aleksandra
Published: November 2022

We investigated gut bacteria from three insect species for the presence of plant growth properties (PGP). Out of 146 bacterial strains obtained from 20 adult specimens of Scolytidae sp., 50 specimens of Oulema melanopus, and 150 specimens of Diabrotica virgifera, we selected 11 strains displaying the following: PGP, phosphate solubility, production of cellulase, siderophore, lipase, protease, and hydrogen cyanide. The strains were tested for growth promotion ability on tomato (Lycopersicon esculentum) plants. Each strain was tested individually, and all strains were tested together as a bacterial consortium. Tomato fruit yield was compared with the negative control. The plants treated with bacterial consortium showed a significant increase in fruit yield, in both number of fruits (+41%) and weight of fruits (+44%). The second highest yield was obtained for treatment with Serratia liquefaciens Dv032 strain, where the number and weight of yielded fruits increased by 35% and 30%, respectively. All selected 11 strains were obtained from Western Corn Rootworm (WCR), Diabrotica virgifera. The consortium comprised: Ewingella americana, Lactococcus garvieae, L. lactis, Pseudomonas putida, Serratia liquefaciens, and S. plymuthica. To our knowledge, this is the first successful application of D. virgifera gut bacteria for tomato plant growth stimulation that has been described.
Towards an In Vitro 3D Model for Photosynthetic Cancer Treatment: A Study of Microalgae and Tumor Cell Interactions
Authors: Holmes Christopher , Varas Juan , San Martín Sebastián , Egaña José Tomás
Published: November 2022

As hypoxic tumors show resistance to several clinical treatments, photosynthetic microorganisms have been recently suggested as a promising safe alternative for oxygenating the tumor microenvironment. The relationship between organisms and the effect microalgae have on tumors is still largely unknown, evidencing the need for a simple yet representative model for studying photosynthetic tumor oxygenation in a reproducible manner. Here, we present a 3D photosynthetic tumor model composed of human melanoma cells and the microalgae Chlamydomonas reinhardtii, both seeded into a collagen scaffold, which allows for the simultaneous study of both cell types. This work focuses on the biocompatibility and cellular interactions of the two cell types, as well as the study of photosynthetic oxygenation of the tumor cells. It is shown that both cell types are biocompatible with one another at cell culture conditions and that a 10:1 ratio of microalgae to cells meets the metabolic requirement of the tumor cells, producing over twice the required amount of oxygen. This 3D tumor model provides an easy-to-use in vitro resource for analyzing the effects of photosynthetically produced oxygen on a tumor microenvironment, thus opening various potential research avenues.
miR-23b-3p, miR-124-3p and miR-218-5p Synergistic or Additive Effects on Cellular Processes That Modulate Cervical Cancer Progression? A Molecular Balance That Needs Attention
Authors: Romero-López Manuel Joaquín , Jiménez-Wences Hilda , Cruz-De la Rosa Merlin Itsel , Román-Fernández Ilce Valeria , Fernández-Tilapa Gloria
Published: November 2022

In cervical cancer (CC), miR-23b-3p, miR-124-3p, and miR-218-5p have been found to act as tumor suppressors by regulating cellular processes related to progression and metastasis. The objective of the present review is to provide an update on the experimental evidence about the role of miR-23b-3p, miR-124-3p, and miR-218-5p in the regulation of CC progression. Additionally, we present the results of a bioinformatic analysis that suggest that these miRNAs have a somewhat redundant role in the same cellular processes that may result in a synergistic effect to promote CC progression. The results indicate that specific and common target genes for miR-23b-3p, miR-124-3p, and miR-218-5p regulate proliferation, migration, apoptosis, and angiogenesis, all processes that are related to CC maintenance and progression. Furthermore, several target genes may regulate cancer-related signaling pathways. We found that a total of 271 proteins encoded by the target mRNAs of miR-23b-3p, miR-124-3p, or miR-218-5p interact to regulate the cellular processes previously mentioned, and some of these proteins are regulated by HPV-16 E7. Taken together, information analysis indicates that miR-23b-3p, miR-124-3p, and miR-218-5p may potentiate their effects to modulate the cellular processes related to the progression and maintenance of CC with and without HPV-16 involvement.
New Positive TRPC6 Modulator Penetrates Blood–Brain Barrier, Eliminates Synaptic Deficiency and Restores Memory Deficit in 5xFAD Mice
Authors: Zernov Nikita , Veselovsky Alexander V. , Poroikov Vladimir V. , Melentieva Daria , Bolshakova Anastasia , Popugaeva Elena
Published: November 2022

Synapse loss in the brain of Alzheimer’s disease patients correlates with cognitive dysfunctions. Drugs that limit synaptic loss are promising pharmacological agents. The transient receptor potential cation channel, subfamily C, member 6 (TRPC6) regulates the formation of an excitatory synapse. Positive regulation of TRPC6 results in increased synapse formation and enhances learning and memory in animal models. The novel selective TRPC6 agonist, 3-(3-,4-Dihydro-6,7-dimethoxy-3,3-dimethyl-1-isoquinolinyl)-2H-1-benzopyran-2-one, has recently been identified. Here we present in silico, in vitro, ex vivo, pharmacokinetic and in vivo studies of this compound. We demonstrate that it binds to the extracellular agonist binding site of the human TRPC6, protects hippocampal mushroom spines from amyloid toxicity in vitro, efficiently recovers synaptic plasticity in 5xFAD brain slices, penetrates the blood–brain barrier and recovers cognitive deficits in 5xFAD mice. We suggest that C20 might be recognized as the novel TRPC6-selective drug suitable to treat synaptic deficiency in Alzheimer’s disease-affected hippocampal neurons.
A Food-Grade Method for Enhancing the Levels of Low Molecular Weight Proanthocyanidins with Potentially High Intestinal Bioavailability
Authors: Iannuzzo Fortuna , Piccolo Vincenzo , Novellino Ettore , Schiano Elisabetta , Salviati Emanuela , Summa Vincenzo , Campiglia Pietro , Tenore Gian Carlo , Maisto Maria
Published: November 2022

Proanthocyanidins (PACs) are a group of bioactive molecules found in a variety of plants and foods. Their bioavailability depends on their molecular size, with monomers and dimers being more bioavailable than those that have a higher polymerization degree. This study aimed to develop a method to convert high-molecular-weight PACs to low-molecular-weight ones in a grape seed extract (GSE) from Vitis vinifera L. Therefore, GSE was subjected to alkaline treatment (ATGSE), and its difference in chemical composition, compared to GSE, was evaluated using a molecular networking (MN) approach based on results obtained from HPLC-ESI HRMS/MS characterization analysis. The network analysis mainly noted the PAC cluster with about 142 PAC compounds identified. In particular, the obtained results showed a higher content of monomeric and dimeric PACs in ATGSE compared to GSE, with 58% and 49% monomers and 31% and 24% dimers, respectively. Conversely, trimeric (9%), polymeric (4%), and galloylated PACs (14%) were more abundant in GSE than in ATGSE (6%, 1%, and 4%, respectively). Moreover, in vitro antioxidant and anti-inflammatory activities were investigated, showing the high beneficial potential of both extracts. In conclusion, ATGSE could represent an innovative natural matrix rich in bioavailable and bioaccessible PACs for nutraceutical applications with potential beneficial properties.
Natural Products for Esophageal Cancer Therapy: From Traditional Medicine to Modern Drug Discovery
Authors: An Jeongeun , An Soojin , Choi Min , Jung Ji Hoon , Kim Bonglee
Published: November 2022

Esophageal cancer (EC) is one of the most malignant types of cancer worldwide and has a high incidence and mortality rate in Asian countries. When it comes to treating EC, although primary methods such as chemotherapy and surgery exist, the prognosis remains poor. The purpose of this current research is to review the range of effects that natural products have on cancer by analyzing studies conducted on EC. Fifty-seven studies were categorized into four anti-cancer mechanisms, as well as clinical trials. The studies that were scrutinized in this research were all reported within five years. The majority of the substances reviewed induced apoptosis in EC, acting on a variety of mechanisms. Taken together, this study supports the fact that natural products have the potential to act as a candidate for treating EC.
Molecular Genetics of GLUT1DS Italian Pediatric Cohort: 10 Novel Disease-Related Variants and Structural Analysis
Authors: Mauri Alessia , Duse Alessandra , Palm Giacomo , Previtali Roberto , Bova Stefania Maria , Olivotto Sara , Benedetti Sara , Coscia Francesca , Veggiotti Pierangelo , Cereda Cristina
Published: November 2022

GLUT1 deficiency syndrome (GLUT1DS1; OMIM #606777) is a rare genetic metabolic disease, characterized by infantile-onset epileptic encephalopathy, global developmental delay, progressive microcephaly, and movement disorders (e.g., spasticity and dystonia). It is caused by heterozygous mutations in the SLC2A1 gene, which encodes the GLUT1 protein, a glucose transporter across the blood-brain barrier (BBB). Most commonly, these variants arise de novo resulting in sporadic cases, although several familial cases with AD inheritance pattern have been described. Twenty-seven Italian pediatric patients, clinically suspect of GLUT1DS from both sporadic and familial cases, have been enrolled. We detected by trios sequencing analysis 25 different variants causing GLUT1DS. Of these, 40% of the identified variants (10 out of 25) had never been reported before, including missense, frameshift, and splice site variants. Their structural mapping on the X-ray structure of GLUT1 strongly suggested the potential pathogenic effects of these novel disease-related mutations, broadening the genotypic spectrum heterogeneity found in the SLC2A1 gene. Moreover, 24% is located in a vulnerable region of the GLUT1 protein that involves transmembrane 4 and 5 helices encoded by exon 4, confirming a mutational hotspot in the SLC2A1 gene. Lastly, we investigated possible correlations between mutation type and clinical and biochemical data observed in our GLUT1DS cohort, revealing that splice site and frameshift variants are related to a more severe phenotype and low CSF parameters.
MK2 Promotes the Development and Progression of Pancreatic Neuroendocrine Tumors Mediated by Macrophages and Metabolomic Factors
Authors: Jacenik Damian , Lebish Eric J. , Beswick Ellen J.
Published: November 2022

Cases of pancreatic neuroendocrine tumors (PNETs) are growing in number, and new treatment options are needed in order to improve patient outcomes. The mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a crucial regulator of cytokine/chemokine production. The significance of MK2 expression and signaling pathway mediated by MK2 in PNETs has not been investigated. To characterize the impact of MK2 on PNET growth, we used the RipTag2 transgenic murine model of PNETs, and we developed a primary PNET cell line for both in vitro and in vivo studies. In the transgenic murine model of PNETs, we found that MK2 inhibition improves survival of mice and prevents PNET progression. MK2 blockade abolished cytokine/chemokine production, which was related to macrophage function. A role for MK2 in the regulation of metabolic factor secretion in PNETs was identified, making this the first study to identify a potential role for the MK2 pathway in regulation of tumor metabolism. Moreover, using an in vitro approach and allograft model of PNETs, we were able to show that macrophages with MK2 depletion exhibit increased cytotoxicity against PNET cells and substantially decreased production of pro-inflammatory cytokines and chemokines, as well as metabolic factors. Taken together, our work identifies MK2 as a potent driver of immune response and metabolic effectors in PNETs, suggesting it is a potential therapeutic target for patients with PNETs.