bluuebunny/crossref_metadata_2025 huggingface dataset:
Theme Trends and Knowledge-Relationship in Lifestyle Research: A Bibliometric Analysis
Authors: Kim Ah-Ram , Park Hae Yean
Published: July 2021

Healthy living habits (healthy eating, regular physical activity, abstinence from smoking, restrictions on alcohol consumption, and stress management) can help prevent a significant number of diseases. The purpose of this study is to use a bibliometric analysis to analyze the relationships between countries, institutions and authors through lifestyle studies from 2016 to 2020 to find out the latest research trends. This study utilized bibliometric data collected through Scopus including thesis titles, authors, agencies, countries/regions, publication years, and keywords. Data were analyzed using the VOS viewer (Vers. 1.6.13; Leiden University, Leiden, The Netherlands) and the findings were used to visualize similarity mapping techniques. Publication of lifestyle-related research papers has steadily increased between 2016 and 2020. The country/region most actively conducting such research was the United States, also home to the majority of institutions conducting work in the field. PloS ONE published the most lifestyle-related research under the field of Medicine. Identified keywords were related to risk measures, psychosocial factors, prevention, health promotion, and risk factors. Lifestyle research is a promising field of research worldwide and has great potential to improve human health, the environment, and quality of life. The findings are expected to promote future research and give direction to the advancement of the field of research by comprehensively analyzing and summarizing lifestyle research trends.
Cultural Adaptation and Psychometric Properties of the Spanish Version of the Occupational Balance Questionnaire: An Instrument for Occupation-Based Research
Authors: Peral-Gómez Paula , López-Roig Sofía , Pastor-Mira María Ángeles , Abad-Navarro Ester , Valera-Gran Desirée , Håkansson Carita , Wagman Petra
Published: July 2021

Occupational balance (OB) may be a major determinant of health outcomes due to its role in bringing a sense of purpose in the occupations that are personally experienced as a process of getting health and wellness. The Occupational Balance Questionnaire (OBQ) is a reliable instrument for measuring OB, although it has not been adapted and validated in Spain so far; therefore, this study had a double aim: (1) to translate and cross-culturally adapt the original OBQ version into Spanish (OBQ-E); (2) to analyze the psychometric properties for its use in the Spanish population. Standard procedures were used for the cross-adaptation process and pilot testing was carried out using three different samples to extend the applicability of the OBQ-E. Validation measures of the final version of the OBQ-E were conducted in a sample of 219 participants. The OBQ-E showed that items and instructions were culturally appropriate and written clearly. Psychometric testing showed excellent internal consistency (Cronbach’s alpha = 0.87; Guttman split-half coefficient = 0.85), good test–retest reliability (rs (Spearman rho) = 0.73), and acceptable convergent validity (overall status, rs = 0.37; Related Quality of Life, rs = 0.42; Satisfaction with Life Scale, rs = 0.54). The findings suggest that the OBQ-E may be a suitable instrument for assessing OB in the Spanish population; hence, it is a promising tool for epidemiological research that will significantly contribute to the understanding of OB as a health-related factor. Nevertheless, further investigation is also warranted to explore the potentiality of this instrument for clinical purposes.
Adherence to a Lifestyle Exercise and Nutrition Intervention in University Employees during the COVID-19 Pandemic: A Randomized Controlled Trial
Authors: García Pérez de Sevilla Guillermo , Barceló Guido Olga , De la Cruz María de la Paz , Blanco Fernández Ascensión , Alejo Lidia B. , Montero Martínez María , Pérez-Ruiz Margarita
Published: July 2021

Healthy lifestyles should be encouraged in the workplace through the occupational health teams of the companies. The objective of the present study was to evaluate the adherence to a lifestyle intervention carried out in university employees during the COVID-19 pandemic and its impact on health-related quality of life (HrQoL). A randomized controlled trial following the CONSORT guidelines was performed, consisting of three supervised interventions lasting for 18 weeks: an educational intervention on healthy habits, a nutritional intervention, and a telematic aerobic and strength exercise intervention. Lifestyle and HrQoL were analyzed six months post-intervention to assess adherence. Twenty-three middle-aged participants completed the study. The intervention group significantly improved their lifestyle according to the Health Promoting Lifestyle Profile II questionnaire, especially in the categories of Health Responsibility, Physical Activity, and Nutrition, with a large effect size. Sitting time was reduced by 2.5 h per day, with a moderate effect size. Regarding HrQoL, the intervention group showed a clinically significant improvement in the Physical Component Summary. Despite the lockdown and the mobility restrictions caused by the COVID-19 pandemic, this intervention performed on university employees achieved adherence to a healthier lifestyle and improved their HrQoL, which is of great clinical relevance.
Inequalities in Exposure to Ambient Air Neurotoxicants and Disparities in Markers of Neurodevelopment in Children by Maternal Nativity Status
Authors: Araya Faven , Stingone Jeanette A. , Claudio Luz
Published: July 2021

Exposure levels to environmental pollutants vary significantly among different populations. These inequities in exposure to hazardous air pollutants (HAP) among different populations can contribute to disparities in neurodevelopmental outcomes. The aim of this study was to determine if exposure to HAP varies by maternal nativity status, a demographic marker often overlooked in the study of health disparities. We also assessed if those inequalities in exposure levels are associated with neurodevelopmental measures in young children. To do this, we obtained data from the Early Childhood Longitudinal Study-Birth cohort (ECLS-B), a nationally representative sample of children born in the U.S. in the year 2001 (n = 4750). Bayley’s Short Form-Research Edition (BSF-R) was used to measure cognitive development at 2 years of age. Using residential location at nine months of age, participants were assigned exposures to ten HAPs identified as potentially neurotoxic. Linear regression models were used to assess the joint effect of maternal nativity status and HAP exposure on neurodevelopment. Results showed inequities in exposure levels to ten different HAPs among the populations, as approximately 32% of children of foreign-born mothers were exposed to high levels of HAPs, compared to 21% of children born to U.S.-born mothers. Adjusting for socioeconomic factors, both isophorone exposure (a marker of industrial pollution) (−0.04, 95% CI, −0.12, 0.04) and maternal nativity status (−0.17, 95% CI, −0.27, −0.06) were independently associated with lower standardized BSF-R mental scores in children. Interaction between nativity status and isophorone was not statistically significant, but the change in mental scores associated with isophorone exposure was greater in children of foreign-born mothers compared to children of U.S.-born mothers (−0.12, vs. −0.03, p = 0.2). In conclusion, exposure to HAPs within the highest quartile was more commonly found among children of foreign-born mothers as compared to children of US-born mothers, indicating inequities in pollutant exposure by nativity status within urban populations. Exposures associated with nativity status may negatively contribute to children’s neurodevelopment.
Changes in Types of Drinking Behavior in Korean Adults: Differences in Demographics, Depression, and Suicidal Thoughts
Authors: Son Hye-Gyeong , Jeong Kyu-Hyoung , Cho Heeran J. , Lee Minuk
Published: July 2021

Background: Longitudinal studies of drinking behavior have reported inconsistent changes in drinking behavior as people age. Thus, this study aims to characterize the changes in drinking behavior among Korean adults and to reveal differences in their demographics, depression, and suicidal thoughts. Methods: This study used the Korea Welfare Panel Study data over nine years (2009 to 2017), analyzing a total of 7506 participants. Growth mixture modeling was applied to classify patterns of change in drinking in these participants. The χ2 test and analysis of variance were used to analyze the differences in demographics, depression, and suicidal thoughts according to patterns of change in drinking. Results: Changes in drinking among Korean adults were categorized into four types: “high-risk retention”, “medium-risk to high-risk”, “high-risk to low-risk”, and “low-risk retention”. Gender, age, education, marital status, living arrangement, living area, and depression differed among these groups. Conclusion: We identified four types of changes in adult drinking behavior in South Korea, which varied in their demographics and depression levels. These results suggest that tailoring interventions to the type of behavioral changes might be more useful than batch interventions.
Sentinel 2 Time Series Analysis with 3D Feature Pyramid Network and Time Domain Class Activation Intervals for Crop Mapping
Authors: Gallo Ignazio , La Grassa Riccardo , Landro Nicola , Boschetti Mirco
Published: July 2021

In this paper, we provide an innovative contribution in the research domain dedicated to crop mapping by exploiting the of Sentinel-2 satellite images time series, with the specific aim to extract information on “where and when” crops are grown. The final goal is to set up a workflow able to reliably identify (classify) the different crops that are grown in a given area by exploiting an end-to-end (3+2)D convolutional neural network (CNN) for semantic segmentation. The method also has the ambition to provide information, at pixel level, regarding the period in which a given crop is cultivated during the season. To this end, we propose a solution called Class Activation Interval (CAI) which allows us to interpret, for each pixel, the reasoning made by CNN in the classification determining in which time interval, of the input time series, the class is likely to be present or not. Our experiments, using a public domain dataset, show that the approach is able to accurately detect crop classes with an overall accuracy of about 93% and that the network can detect discriminatory time intervals in which crop is cultivated. These results have twofold importance: (i) demonstrate the ability of the network to correctly interpret the investigated physical process (i.e., bare soil condition, plant growth, senescence and harvesting according to specific cultivated variety) and (ii) provide further information to the end-user (e.g., the presence of crops and its temporal dynamics).
Advances in the Chemistry of Porphyrins and Related Macrocycles
Authors: Romeo Andrea , Castriciano Maria Angela , Scolaro Luigi Monsù
Published: July 2021

Porphyrins and their analogues feature remarkably in nature, being prosthetic groups in a wide variety of primary metabolites playing a pivotal role in many biological processes [...]
Generating Cloned Goats by Somatic Cell Nuclear Transfer—Molecular Determinants and Application to Transgenics and Biomedicine
Authors: Skrzyszowska Maria , Samiec Marcin
Published: July 2021

The domestic goat (Capra aegagrus hircus), a mammalian species with high genetic merit for production of milk and meat, can be a tremendously valuable tool for transgenic research. This research is focused on the production and multiplication of genetically engineered or genome-edited cloned specimens by applying somatic cell nuclear transfer (SCNT), which is a dynamically developing assisted reproductive technology (ART). The efficiency of generating the SCNT-derived embryos, conceptuses, and progeny in goats was found to be determined by a variety of factors controlling the biological, molecular, and epigenetic events. On the one hand, the pivotal objective of our paper was to demonstrate the progress and the state-of-the-art achievements related to the innovative and highly efficient solutions used for the creation of transgenic cloned does and bucks. On the other hand, this review seeks to highlight not only current goals and obstacles but also future challenges to be faced by the approaches applied to propagate genetically modified SCNT-derived goats for the purposes of pharmacology, biomedicine, nutritional biotechnology, the agri-food industry, and modern livestock breeding.
Applying Proteomics and Integrative “Omics” Strategies to Decipher the Chronic Kidney Disease-Related Atherosclerosis
Authors: Tracz Joanna , Luczak Magdalena
Published: July 2021

Patients with chronic kidney disease (CKD) are at increased risk of atherosclerosis and premature mortality, mainly due to cardiovascular events. However, well-known risk factors, which promote “classical” atherosclerosis are alone insufficient to explain the high prevalence of atherosclerosis-related to CKD (CKD-A). The complexity of the molecular mechanisms underlying the acceleration of CKD-A is still to be defied. To obtain a holistic picture of these changes, comprehensive proteomic approaches have been developed including global protein profiling followed by functional bioinformatics analyses of dysregulated pathways. Furthermore, proteomics surveys in combination with other “omics” techniques, i.e., transcriptomics and metabolomics as well as physiological assays provide a solid ground for interpretation of observed phenomena in the context of disease pathology. This review discusses the comprehensive application of various “omics” approaches, with emphasis on proteomics, to tackle the molecular mechanisms underlying CKD-A progression. We summarize here the recent findings derived from global proteomic approaches and underline the potential of utilizing integrative systems biology, to gain a deeper insight into the pathogenesis of CKD-A and other disorders.
The Multifactorial Progression from the Islet Autoimmunity to Type 1 Diabetes in Children
Authors: Bauer Witold , Gyenesei Attila , Krętowski Adam
Published: July 2021

Type 1 Diabetes (T1D) results from autoimmune destruction of insulin producing pancreatic ß-cells. This disease, with a peak incidence in childhood, causes the lifelong need for insulin injections and necessitates careful monitoring of blood glucose levels. However, despite the current insulin therapies, it still shortens life expectancy due to complications affecting multiple organs. Recently, the incidence of T1D in childhood has increased by 3–5% per year in most developed Western countries. The heterogeneity of the disease process is supported by the findings of follow-up studies started early in infancy. The development of T1D is usually preceded by the appearance of autoantibodies targeted against antigens expressed in the pancreatic islets. The risk of T1D increases significantly with an increasing number of positive autoantibodies. The order of autoantibody appearance affects the disease risk. Genetic susceptibility, mainly defined by the human leukocyte antigen (HLA) class II gene region and environmental factors, is important in the development of islet autoimmunity and T1D. Environmental factors, mainly those linked to the changes in the gut microbiome as well as several pathogens, especially viruses, and diet are key modulators of T1D. The aim of this paper is to expand the understanding of the aetiology and pathogenesis of T1D in childhood by detailed description and comparison of factors affecting the progression from the islet autoimmunity to T1D in children.
Carnosine Protects against Cerebral Ischemic Injury by Inhibiting Matrix-Metalloproteinases
Authors: Kim Eun-Hye , Kim Eun-Sun , Shin Donggeun , Kim Donghyun , Choi Sungbin , Shin Young-Jun , Kim Kyeong-A , Noh Dabi , Caglayan Ahmet B. , Rajanikant G.K. , Majid Arshad , Bae Ok-Nam
Published: July 2021

Stroke is one of the leading causes of death and disability worldwide. However, treatment options for ischemic stroke remain limited. Matrix-metalloproteinases (MMPs) contribute to brain damage during ischemic strokes by disrupting the blood-brain barrier (BBB) and causing brain edemas. Carnosine, an endogenous dipeptide, was found by us and others to be protective against ischemic brain injury. In this study, we investigated whether carnosine influences MMP activity. Brain MMP levels and activity were measured by gelatin zymography after permanent occlusion of the middle cerebral artery (pMCAO) in rats and in vitro enzyme assays. Carnosine significantly reduced infarct volume and edema. Gelatin zymography and in vitro enzyme assays showed that carnosine inhibited brain MMPs. We showed that carnosine inhibited both MMP-2 and MMP-9 activity by chelating zinc. Carnosine also reduced the ischemia-mediated degradation of the tight junction proteins that comprise the BBB. In summary, our findings show that carnosine inhibits MMP activity by chelating zinc, an essential MMP co-factor, resulting in the reduction of edema and brain injury. We believe that our findings shed new light on the neuroprotective mechanism of carnosine against ischemic brain damage.
Novel Hybrid Compounds Containing Benzofuroxan and Aminothiazole Scaffolds: Synthesis and Evaluation of Their Anticancer Activity
Authors: Chugunova Elena , Micheletti Gabriele , Telese Dario , Boga Carla , Islamov Daut , Usachev Konstantin , Burilov Alexander , Tulesinova Alena , Voloshina Alexandra , Lyubina Anna , Amerhanova Syumbelya , Gerasimova Tatiana , Gilfanova Aisylu , Syakaev Victor
Published: July 2021

A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.
In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver
Authors: Oke Shelby L. , Lee Kendrick , Papp Rosemary , Laviolette Steven R. , Hardy Daniel B.
Published: July 2021

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.
Synthesis of Vertically Aligned Porous Silica Thin Films Functionalized by Silver Ions
Authors: Fedorchuk Andrii , Walcarius Alain , Laskowska Magdalena , Vila Neus , Kowalczyk Paweł , Cpałka Krzysztof , Laskowski Łukasz
Published: July 2021

In this work, we have developed a chemical procedure enabling the preparation of highly ordered and vertically aligned mesoporous silica films containing selected contents of silver ions bonded inside the mesopore channels via anchoring propyl-carboxyl units. The procedure involves the electrochemically assisted self-assembly co-condensation of tetraethoxysilane and (3-cyanopropyl)triethoxysilane in the presence of cetyltrimethylammonium bromide as a surfactant, the subsequent hydrolysis of cyano groups into carboxylate ones, followed by their complexation with silver ions. The output materials have been electrochemically characterized with regard to the synthesis effectiveness in order to confirm and quantify the presence of the silver ions in the material. The mesostructure has been observed by transmission electron microscopy. We have pointed out that it is possible to finely tune the functionalization level by controlling the co-condensation procedure, notably the concentration of (3-cyanopropyl)triethoxysilane in the synthesis medium.
Reelin Affects Signaling Pathways of a Group of Inhibitory Neurons and the Development of Inhibitory Synapses in Primary Neurons
Authors: Lee Seong-Eun , Lee Gum Hwa
Published: July 2021

Reelin is a secretory protein involved in a variety of processes in forebrain development and function, including neuronal migration, dendrite growth, spine formation, and synaptic plasticity. Most of the function of Reelin is focused on excitatory neurons; however, little is known about its effects on inhibitory neurons and inhibitory synapses. In this study, we investigated the phosphatidylinositol 3-kinase/Akt pathway of Reelin in primary cortical and hippocampal neurons. Individual neurons were visualized using immunofluorescence to distinguish inhibitory neurons from excitatory neurons. Reelin-rich protein supplementation significantly induced the phosphorylation of Akt and ribosomal S6 protein in excitatory neurons, but not in most inhibitory neurons. In somatostatin-expressing inhibitory neurons, one of major subtypes of inhibitory neurons, Reelin-rich protein supplementation induced the phosphorylation of S6. Subsequently, we investigated whether or not Reelin-rich protein supplementation affected dendrite development in cultured inhibitory neurons. Reelin-rich protein supplementation did not change the total length of dendrites in inhibitory neurons in vitro. Finally, we examined the development of inhibitory synapses in primary hippocampal neurons and found that Reelin-rich protein supplementation significantly reduced the density of gephyrin–VGAT-positive clusters in the dendritic regions without changing the expression levels of several inhibitory synapse-related proteins. These findings indicate a new role for Reelin in specific groups of inhibitory neurons and the development of inhibitory synapses, which may contribute to the underlying cellular mechanisms of RELN-associated neurological disorders.
Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model
Authors: Byun Eui-Baek , Song Ha-Yeon , Kim Woo Sik , Han Jeong Moo , Seo Ho Seong , Park Sang-Hyun , Kim Kwangwook , Byun Eui-Hong
Published: July 2021

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.
The Intrinsic Nutrient Sensing Adipokinetic Hormone Producing Cells Function in Modulation of Metabolism, Activity, and Stress
Authors: Nelson Jonathan M. , Saunders Cecil J. , Johnson Erik C.
Published: July 2021

All organisms confront the challenges of maintaining metabolic homeostasis in light of both variabilities in nutrient supplies and energetic costs of different physiologies and behaviors. While all cells are nutrient sensitive, only relative few cells within Metazoans are nutrient sensing cells. Nutrient sensing cells organize systemic behavioral and physiological responses to changing metabolic states. One group of cells present in the arthropods, is the adipokinetic hormone producing cells (APCs). APCs possess intrinsic nutrient sensors and receive contextual information regarding metabolic state through other endocrine connections. APCs express receptors for different hormones which modulate APC physiology and the secretion of the adipokinetic hormone (AKH). APCs are functionally similar to alpha cells in the mammalian pancreas and display a similar physiological organization. AKH release results in both hypertrehalosemia and hyperlipidemia through high affinity binding to the AKH receptor (AKHR). Another hallmark of AKH signaling is heightened locomotor activity, which accompanies starvation and is thought to enhance foraging. In this review, we discuss mechanisms of nutrient sensing and modulation of AKH release. Additionally, we compare the organization of AKH/AKHR signaling in different taxa. Lastly, we consider the signals that APCs integrate as well as recent experimental results that have expanded the functional repertoire of AKH signaling, further establishing this as both a metabolic and stress hormone.
Deficiency of IL-27 Signaling Exacerbates Experimental Autoimmune Uveitis with Elevated Uveitogenic Th1 and Th17 Responses
Authors: Wu Sihan , Ma Rui , Zhong Yajie , Chen Zilin , Zhou Hongyan , Zhou Minyi , Chong Waipo , Chen Jun
Published: July 2021

Human uveitis is an autoimmune disease of the central nervous system that is characterized by ocular inflammation with the involvement of uveitogenic Th1 and Th17 responses. In experimental autoimmune uveitis (EAU), the animal model for human uveitis, both responses are proven to be critical in disease development. Therefore, targeting both Th1 and Th17 cells has therapeutic implication for disease resolution. IL-27 is a multifunctional cytokine that can either promote or inhibit T cell responses and is implicated in both autoimmune and infectious diseases. The aim of this study is to characterize the role of IL-27/IL-27R signaling in regulating uveitogenic Th1/Th17 responses in EAU. By immunizing IL-27Rα−/− mice and their wild-type (WT) littermates for EAU, we demonstrated that IL-27 signaling deficiency exacerbated EAU with severe ocular inflammation and impairment of visual function. Furthermore, there was a significant increase in the eye-infiltrating Th1 and Th17 cells in IL-27Rα−/− EAU mice compared to WT. Their retinal antigen-specific Th1 and Th17 responses were also significantly increased, as represented by the elevation of their signature cytokines, IFN-γ and IL-17A, respectively. We also observed the upregulation of another pathogenic cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), from effector T cells in IL-27Rα−/− EAU mice. Mechanistic studies confirmed that IL-27 inhibited GM-CSF production from Th17 cells. In addition, the induction of IL-10 producing type 1 regulatory T (Tr1) cells was impaired in IL-27Rα−/− EAU mice. These results identified that IL-27 signaling plays a suppressive role in EAU by regulating multiple CD4+ cell subsets, including the effector Th1 and Th17 cells and the regulatory Tr1 cells. Our findings provide new insights for therapeutic potential in controlling uveitis by enhancing IL-27 signaling.
Mercury Toxicity and Neurogenesis in the Mammalian Brain
Authors: Abbott Louise C. , Nigussie Fikru
Published: July 2021

The mammalian brain is formed from billions of cells that include a wide array of neuronal and glial subtypes. Neural progenitor cells give rise to the vast majority of these cells during embryonic, fetal, and early postnatal developmental periods. The process of embryonic neurogenesis includes proliferation, differentiation, migration, the programmed death of some newly formed cells, and the final integration of differentiated neurons into neural networks. Adult neurogenesis also occurs in the mammalian brain, but adult neurogenesis is beyond the scope of this review. Developing embryonic neurons are particularly susceptible to neurotoxicants and especially mercury toxicity. This review focused on observations concerning how mercury, and in particular, methylmercury, affects neurogenesis in the developing mammalian brain. We summarized information on models used to study developmental mercury toxicity, theories of pathogenesis, and treatments that could be used to reduce the toxic effects of mercury on developing neurons.
Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure
Authors: Nedeljković Marko , Sastre Diego , Sundberg Eric
Published: July 2021

The bacterial flagellum is a complex and dynamic nanomachine that propels bacteria through liquids. It consists of a basal body, a hook, and a long filament. The flagellar filament is composed of thousands of copies of the protein flagellin (FliC) arranged helically and ending with a filament cap composed of an oligomer of the protein FliD. The overall structure of the filament core is preserved across bacterial species, while the outer domains exhibit high variability, and in some cases are even completely absent. Flagellar assembly is a complex and energetically costly process triggered by environmental stimuli and, accordingly, highly regulated on transcriptional, translational and post-translational levels. Apart from its role in locomotion, the filament is critically important in several other aspects of bacterial survival, reproduction and pathogenicity, such as adhesion to surfaces, secretion of virulence factors and formation of biofilms. Additionally, due to its ability to provoke potent immune responses, flagellins have a role as adjuvants in vaccine development. In this review, we summarize the latest knowledge on the structure of flagellins, capping proteins and filaments, as well as their regulation and role during the colonization and infection of the host.
Tbx21 and Foxp3 Are Epigenetically Stabilized in T-Bet+ Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs
Authors: Elfaki Yassin , Yang Juhao , Boehme Julia , Schultz Kristin , Bruder Dunja , Falk Christine S. , Huehn Jochen , Floess Stefan
Published: July 2021

During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet− Tregs are epigenetically stabilized during IAV-induced infection in the lung.
Mitochondrial Metal Ion Transport in Cell Metabolism and Disease
Authors: Wang Xuan , An Peng , Gu Zhenglong , Luo Yongting , Luo Junjie
Published: July 2021

Mitochondria are vital to life and provide biological energy for other organelles and cell physiological processes. On the mitochondrial double layer membrane, there are a variety of channels and transporters to transport different metal ions, such as Ca2+, K+, Na+, Mg2+, Zn2+ and Fe2+/Fe3+. Emerging evidence in recent years has shown that the metal ion transport is essential for mitochondrial function and cellular metabolism, including oxidative phosphorylation (OXPHOS), ATP production, mitochondrial integrity, mitochondrial volume, enzyme activity, signal transduction, proliferation and apoptosis. The homeostasis of mitochondrial metal ions plays an important role in maintaining mitochondria and cell functions and regulating multiple diseases. In particular, channels and transporters for transporting mitochondrial metal ions are very critical, which can be used as potential targets to treat neurodegeneration, cardiovascular diseases, cancer, diabetes and other metabolic diseases. This review summarizes the current research on several types of mitochondrial metal ion channels/transporters and their functions in cell metabolism and diseases, providing strong evidence and therapeutic strategies for further insights into related diseases.
MicroRNAs in Epithelial–Mesenchymal Transition Process of Cancer: Potential Targets for Chemotherapy
Authors: Peng Fu , Fan Huali , Li Sui , Peng Cheng , Pan Xiaoqi
Published: July 2021

In the last decades, a kind of small non-coding RNA molecules, called as microRNAs, has been applied as negative regulators in various types of cancer treatment through down-regulation of their targets. More recent studies exert that microRNAs play a critical role in the EMT process of cancer, promoting or inhibiting EMT progression. Interestingly, accumulating evidence suggests that pure compounds from natural plants could modulate deregulated microRNAs to inhibit EMT, resulting in the inhibition of cancer development. This small essay is on the purpose of demonstrating the significance and function of microRNAs in the EMT process as oncogenes and tumor suppressor genes according to studies mainly conducted in the last four years, providing evidence of efficient target therapy. The review also summarizes the drug candidates with the ability to restrain EMT in cancer through microRNA regulation.
Development of Polypyrrole Modified Screen-Printed Carbon Electrode Based Sensors for Determination of L-Tyrosine in Pharmaceutical Products
Authors: Dinu Ancuța , Apetrei Constantin
Published: July 2021

Good health, of vital importance in order to carry out our daily routine, consists of both physical and mental health. Tyrosine (Tyr) deficiency as well as its excess are issues that can affect mental health and can generate disorders such as depression, anxiety, or stress. Tyr is the amino acid (AA) responsible for maintaining good mental health, and for this reason, the present research presents the development of new electrochemical sensors modified with polypyrrole (PPy) doped with different doping agents such as potassium hexacyanoferrate (II) (FeCN), sodium nitroprusside (NP), and sodium dodecyl sulfate (SDS) for a selective and sensitive detection of Tyr. The development of the sensors was carried out by chronoamperometry (CA) and the electrochemical characterization was carried out by cyclic voltammetry (CV). The detection limits (LOD) obtained with each modified sensor were 8.2 × 10−8 M in the case of PPy /FeCN-SPCE, 4.3 × 10−7 M in the case of PPy/NP-SPCE, and of 3.51 × 10−7 M in the case of PPy/SDS-SPCE, thus demonstrating a good sensitivity of these sensors detecting L-Tyr. The validation of sensors was carried out through quantification of L-Tyr from three pharmaceutical products by the standard addition method with recoveries in the range 99.92–103.97%. Thus, the sensors present adequate selectivity and can be used in the pharmaceutical and medical fields.
The Mandibular and Hyoid Arches—From Molecular Patterning to Shaping Bone and Cartilage
Authors: Fabik Jaroslav , Psutkova Viktorie , Machon Ondrej
Published: July 2021

The mandibular and hyoid arches collectively make up the facial skeleton, also known as the viscerocranium. Although all three germ layers come together to assemble the pharyngeal arches, the majority of tissue within viscerocranial skeletal components differentiates from the neural crest. Since nearly one third of all birth defects in humans affect the craniofacial region, it is important to understand how signalling pathways and transcription factors govern the embryogenesis and skeletogenesis of the viscerocranium. This review focuses on mouse and zebrafish models of craniofacial development. We highlight gene regulatory networks directing the patterning and osteochondrogenesis of the mandibular and hyoid arches that are actually conserved among all gnathostomes. The first part of this review describes the anatomy and development of mandibular and hyoid arches in both species. The second part analyses cell signalling and transcription factors that ensure the specificity of individual structures along the anatomical axes. The third part discusses the genes and molecules that control the formation of bone and cartilage within mandibular and hyoid arches and how dysregulation of molecular signalling influences the development of skeletal components of the viscerocranium. In conclusion, we notice that mandibular malformations in humans and mice often co-occur with hyoid malformations and pinpoint the similar molecular machinery controlling the development of mandibular and hyoid arches.
Cera Flava Alleviates Atopic Dermatitis by Activating Skin Barrier Function via Immune Regulation
Authors: Park Gunhyuk , Moon Byeong Cheol , Choi Goya , Lim Hye-Sun
Published: July 2021

Cera Flava (CF), a natural extract obtained from beehives, is widely used in dermatological products owing to its wound healing, wrinkle reduction, UV-protective, and skin cell turnover stimulation effects. However, its effect on AD-like skin lesions is unknown. In this study, we used a mouse model of AD to evaluate the effects of CP at the molecular and phenotypic levels. Topical house dust mite (HDM) sensitization and challenge were performed on the dorsal skin of NC/Nga mice to induce AD-like cutaneous lesions, phenotypes, and immunologic responses. The topical application of CF for 6 weeks relieved HDM-induced AD-like phenotypes, as quantified by the dermatitis severity score, scratching frequency, and skin moisture. CP decreased immunoglobulin E, histamine, and thymic stromal lymphopoietin levels. Histopathological analysis showed that CF decreased epidermal thickening and the number of mast cells. CF attenuated HDM-induced changes in the expression of skin barrier-related proteins. Furthermore, CF decreased the mRNA levels of inflammatory factors, including interleukin (IL)-1β, IL-4, IL-13, IL-8, TARC, MDC, and RANTES, in dorsal skin tissue via the TLR2/MyD88/TRAF6/ERK pathway. CF influences skin barrier function and immune regulation to alleviate AD symptoms. It may therefore be an effective alternative to topical steroids for the treatment of AD.
Mycobacterium tuberculosis RpfE-Induced Prostaglandin E2 in Dendritic Cells Induces Th1/Th17 Cell Differentiation
Authors: Park Hye-Soo , Choi Seunga , Back Yong-Woo , Lee Kang-In , Choi Han-Gyu , Kim Hwa-Jung
Published: July 2021

Prostaglandin E2 (PGE2) is an important biological mediator involved in the defense against Mycobacterium tuberculosis (Mtb) infection. Currently, there are no reports on the mycobacterial components that regulate PGE2 production. Previously, we have reported that RpfE-treated dendritic cells (DCs) effectively expanded the Th1 and Th17 cell responses simultaneously; however, the mechanism underlying Th1 and Th17 cell differentiation is unclear. Here, we show that PGE2 produced by RpfE-activated DCs via the MAPK and cyclooxygenase 2 signaling pathways induces Th1 and Th17 cell responses mainly via the EP4 receptor. Furthermore, mice administered intranasally with PGE2 displayed RpfE-induced antigen-specific Th1 and Th17 responses with a significant reduction in bacterial load in the lungs. Furthermore, the addition of optimal PGE2 amount to IL-2-IL-6-IL-23p19-IL-1β was essential for promoting differentiation into Th1/Th17 cells with strong bactericidal activity. These results suggest that RpfE-matured DCs produce PGE2 that induces Th1 and Th17 cell differentiation with potent anti-mycobacterial activity.
Genome-Wide Identification and Analysis of the Polycomb Group Family in Medicago truncatula
Authors: Zhao Yuanyuan , Zhang Junchao , Sun Zhanmin , Tang Yixiong , Wu Yanmin
Published: July 2021

Polycomb group (PcG) proteins, which are important epigenetic regulators, play essential roles in the regulatory networks involved in plant growth, development, and environmental stress responses. Currently, as far as we know, no comprehensive and systematic study has been carried out on the PcG family in Medicago truncatula. In the present study, we identified 64 PcG genes with distinct gene structures from the M. truncatula genome. All of the PcG genes were distributed unevenly over eight chromosomes, of which 26 genes underwent gene duplication. The prediction of protein interaction network indicated that 34 M. truncatula PcG proteins exhibited protein–protein interactions, and MtMSI1;4 and MtVRN2 had the largest number of protein–protein interactions. Based on phylogenetic analysis, we divided 375 PcG proteins from 27 species into three groups and nine subgroups. Group I and Group III were composed of five components from the PRC1 complex, and Group II was composed of four components from the PRC2 complex. Additionally, we found that seven PcG proteins in M. truncatula were closely related to the corresponding proteins of Cicer arietinum. Syntenic analysis revealed that PcG proteins had evolved more conservatively in dicots than in monocots. M. truncatula had the most collinearity relationships with Glycine max (36 genes), while collinearity with three monocots was rare (eight genes). The analysis of various types of expression data suggested that PcG genes were involved in the regulation and response process of M. truncatula in multiple developmental stages, in different tissues, and for various environmental stimuli. Meanwhile, many differentially expressed genes (DEGs) were identified in the RNA-seq data, which had potential research value in further studies on gene function verification. These findings provide novel and detailed information on the M. truncatula PcG family, and in the future it would be helpful to carry out related research on the PcG family in other legumes.
IgA Vasculitis: Etiology, Treatment, Biomarkers and Epigenetic Changes
Authors: Sugino Hitomi , Sawada Yu , Nakamura Motonobu
Published: July 2021

IgA, previously called Henoch-Schönlein vasculitis, is an essential immune component that drives the host immune response to the external environment. As IgA has the unique characteristic of a flexible response to broad types of microorganisms, it sometimes causes an autoreactive response in the host human body. IgA vasculitis and related organ dysfunction are representative IgA-mediated autoimmune diseases; bacterial and viral infections often trigger IgA vasculitis. Recent drug developments and the presence of COVID-19 have revealed that these agents can also trigger IgA vasculitis. These findings provide a novel understanding of the pathogenesis of IgA vasculitis. In this review, we focus on the characteristics of IgA and symptoms of IgA vasculitis and other organ dysfunction. We also mention the therapeutic approach, biomarkers, novel triggers for IgA vasculitis, and epigenetic modifications in patients with IgA vasculitis.
Structural Identification of the Pacemaker Cells and Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels in the Heart of the Wild Atlantic Cod, Gadus morhua (Linnaeus, 1758)
Authors: Capillo Gioele , Lauriano Eugenia R. , Icardo Jose M. , Siriyappagouder Prabhugouda , Kuciel Michal , Karapanagiotis Stelios , Zaccone Giacomo , Fernandes Jorge M. O.
Published: July 2021

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are proteins that contain highly conserved functional domains and sequence motifs that are correlated with their unique biophysical activities, to regulate cardiac pacemaker activity and synaptic transmission. These pacemaker proteins have been studied in mammalian species, but little is known now about their heart distribution in lower vertebrates and c-AMP modulation. Here, we characterized the pacemaker system in the heart of the wild Atlantic cod (Gadus morhua), with respect to primary pacemaker molecular markers. Special focus is given to the structural, ultrastructural and molecular characterization of the pacemaker domain, through the expression of HCN channel genes and the immunohistochemistry of HCN isoforms, including the location of intracardiac neurons that are adjacent to the sinoatrial region of the heart. Similarly to zebrafish and mammals, these neurons are immunoreactive to ChAT, VAChT and nNOS. It has been shown that cardiac pacemaking can be modulated by sympathetic and parasympathetic pathways, and the existence of intracardiac neurons projecting back to the central nervous system provide a plausible link between them.