bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Agricultural Sustainability and Green GDP in China: An Emergy Analysis
Authors: Hu Jiangfeng , Lyu Jingjing , Zhang Xinyuan
Published: December 2022

Agricultural sustainability is the foundation and a guarantee of sustainable human reproduction. The scientific assessment of China’s agricultural sustainability is a prerequisite for properly resolving the conflict between short-term economic interests and long-term ecological security. This paper uses the emergy analysis method to estimate agricultural sustainability in China and further calculates the agricultural environmental cost and green GDP. The results show that China’s agricultural emergy yield rate (EYR) is generally greater than 1. This means that more emergy is obtained in relation to renewable and non-renewable inputs from human activity, which also indicates that China’s agricultural agroecosystem is characteristic of a profound transition from a self-supporting tradition to a modern industry based on external economic resource consumption. In contrast, China’s agricultural growth is mainly driven by the input of a large amount of non-renewable resources, which makes the environmental loading rate (ELR) increase year by year, resulting in the deterioration of China’s agricultural emergy sustainability index (ESI). China’s agricultural green GDP accounts for about 94.4% of traditional GDP, which means that the average agricultural environmental cost is about 5.6%, mainly from land loss, accounting for 48.23% of the environmental cost.
Preventive Care and Outcomes of Interprofessional Medicare Annual Wellness Visits for Older Adults
Authors: Masuda Camlyn , Aggarwal Lovedhi , Bray Michele Lani , Cheung Christabel K. , Kim Bum Jung , Wen Aida , Okamoto Lauren , Uechi Matthew , Lee Yeonjung Jane , Masaki Kamal
Published: December 2022

As we anticipate a growing population of older adults, we will see an increase in chronic conditions such as dementia and falls. To meet these public health needs, we must systematically provide screening, education, preventive care, and supportive care for older patients and their caregivers in a primary care setting. This will require a workforce trained in providing for the complex medical and psychosocial needs of an older adult population in an interprofessional and collaborative fashion. By integrating geriatric screening tools into an interdisciplinary Annual Wellness Visit teaching clinic, we were able to successfully improve rates of geriatric screening for dementia, depression, falls, medication reconciliation and advance care planning. We also saw improvements in patient care and satisfaction and provided the opportunity for interprofessional collaboration and education for students in medicine, nursing, pharmacy and social work.
Rasch Modelling to Assess Psychometric Validation of the Knowledge about Tuberculosis Questionnaire (KATUB-Q) for the General Population in Indonesia
Authors: Kusuma Ikhwan Yuda , Triwibowo Deny Nugroho , Pratiwi Arik Dian Eka , Pitaloka Dian Ayu Eka
Published: December 2022

Objective: This study aims to validate and evaluate the psychometric properties of the knowledge about tuberculosis questionnaire (KATUB-Q) for the general population in Indonesia. Methods: The KATUB-Q consists of three domains: general knowledge, transmission, and treatment, with 20 dichotomous items. Rasch analysis through WINSTEPS was used. Results: A total of 504 respondents from 34 provinces in Indonesia completed the survey. Based on the model fit statistics, 3 misfit items were deleted and 17 items were used. Item and person reliability, as well as Cronbach’s Alpha values were 0.99, 0.63, and 0.73, respectively, which means they achieved the minimum acceptable limit of 0.6. Based on the results, Indonesia’s Person ability analysis indicated a high level of knowledge. KATUB-Q has no significant bias item based on sex found in the differential item functioning analysis. Conclusion: KATUB-Q has 17 items with a valid and reliable instrument; hence, it can be used to measure the knowledge about TB in the general population. Practice implications: The unidimensional structure of the core items of the KATUB-Q provides empirical evidence for using the sum score of the items in practice to evaluate the effectiveness of TB education in the general population.
Meaning in Life among Older Adults: An Integrative Model
Authors: Greenblatt-Kimron Lee , Kagan Maya , Zychlinski Ester
Published: December 2022

Meaning in life (MIL) among older adults has a significant physical and mental health impact. This study aimed to present an integrative model of factors that contribute to variability in MIL among older adults, including background characteristics (gender, age, employment status, religiosity), personality characteristics (locus of control, self-efficacy, optimism), and psycho-social factors (psychological distress and loneliness). Participants (751 older adults, Mage = 72.27, SD = 6.28; 446 female, 305 male) responded to a questionnaire in-person or online. Measures included: demographic variables, Short Scale for the Assessment of Locus of Control, New General Self-Efficacy Scale, Life Orientation Test–Revised, Kessler Psychological Distress Scale, and Hughes Short Scale for Measuring Loneliness. Hierarchical regression revealed that younger and religious older adults reported higher MIL levels than older and non-religious older adults. Internal locus of control, higher self-efficacy, and higher optimism were linked to higher MIL levels. Higher psychological distress and loneliness were associated with lower MIL levels, with psychological distress contributing the most of all variables in the study model to explain the variance in MIL among older adults. Employed older old adults reported lower MIL levels than those unemployed. The study emphasizes the importance of an integrative approach in the examination of MIL among older adults.
The Gratitude Resentment and Appreciation Test-Revised Short (GRAT-RS): A Multidimensional Item Response Theory Analysis in Italian Workers
Authors: Svicher Andrea , Palazzeschi Letizia , Gori Alessio , Di Fabio Annamaria
Published: December 2022

Gratitude is a promising resource from a healthy organizational perspective. It is related to many positive outcomes at work. The Gratitude Resentment and Appreciation Test-Revised Short (GRAT-RS) is the most widely used self-report questionnaire to detect gratitude. The present study examined GRAT-RS (the Italian version) by implementing multidimensional item response theory (MIRT) analyses to explore its psychometric properties. The participants were 537 Italian workers. Confirmatory factor analyses (CFA) of the GRAT-RS and MIRT analyses using the Grade Response Model were run. The MIRT discrimination and MIRT difficulty parameters were calculated. A test information function (TIF) and measure of reliability associated with (TIF) scores were also implemented. CFA highlighted that a bifactor model showed the best fit. Hence, MIRT analyses were carried out by implementing a bifactor model. The MIRT bifactor structure showed a good data fit with discrimination parameters ranging from good to excellent and adequate reliability. The good psychometric properties of GRAT-RS were confirmed, highlighting the questionnaire as a reliable tool to measure gratitude in Italian workers.
Catch-Up Growth as a Risk Factor for Rapid Weight Gain, Earlier Menarche and Earlier Pubertal Growth Spurt in Girls Born Small for Gestational Age (SGA)—A Longitudinal Study
Authors: Durda-Masny Magdalena , Stróżewska Weronika , Szwed Anita
Published: December 2022

Most children born small for gestational age (SGA) have rapid postnatal growth. Despite its positive aspects, catch-up growth may affect the level of adipose tissue in the pre-pubertal and pubertal periods and therefore affect the age of puberty. The aim of this study was to determine the associations between size at birth, catch-up growth in infancy, BMI in peripubertal period, age at menarche, and the parameters of adolescent growth spurt of body height in girls born SGA. For 297 girls (22.6% SGA; 77.4% appropriate for gestational age (AGA)) complete body weight and height measurements and age at menarche were obtained. Adolescent growth spurt parameters were estimated using the JPA2 model (AUXAL SSI 3.1). Calculations were made in the Statistica 13 program using the Kruskal-Wallis and Kaplan–Meier tests. Girls born SGA with catch-up had the highest BMIs at the age of 8 years (H = 94.22, p < 0.001) and at menarche (H = 58.21, p < 0.001), experienced menarche earliest (H = 21.77, p < 0.001), same as the onset (H = 6.54, p = 0.012) and peak height velocity (H = 11.71, p = 0.003) of their adolescent growth spurt compared to SGA girls without catch-up and AGA girls. In SGA girls, catch-up growth has far-reaching consequences such as increased risk of fat accumulation and a rapid transition to puberty.
SBAR Method for Improving Well-Being in the Internal Medicine Unit: Quasi-Experimental Research
Authors: Martínez-Fernández María Cristina , Castiñeiras-Martín Sara , Liébana-Presa Cristina , Fernández-Martínez Elena , Gomes Lisa , Marques-Sanchez Pilar
Published: December 2022

SBAR (Situation, Background, Assessment, Recommendation) is a tool for standardizing and improving interprofessional communication. This study aims to explore the impact of SBAR in healthcare professionals’ wellbeing, through concepts such as job satisfaction, engagement, resilience, and job performance, in the internal medicine unit of a university hospital in the province of León (Spain). This is an observational, descriptive, longitudinal case study with a pre- and post-intervention approach. Questionnaires were distributed to a group of doctors, nurses, and healthcare assistants before and after the implementation of the SBAR tool in the ward. The use of SBAR was monitored to ensure staff compliance. Data statistical analysis was performed using the SPSS program. Resilience levels increased significantly post-intervention. Job satisfaction and engagement levels remained neutral, slightly decreasing post-intervention. Besides’ being a useful tool to improve communication, SBAR was effective in improving resilience among staff. Several aspects related to hospital management may have had an impact on job satisfaction and engagement results.
Characterization of Metallic Off-Flavors in Drinking Water: Health, Consumption, and Sensory Perception
Authors: Mirlohi Susan
Published: December 2022

Characterization of taste- and flavor-producing metals, namely iron and copper, in drinking water is a multifaceted subject. Both metals are essential nutrients, can be toxic, and are known to produce unpleasant tastes and flavor sensations in drinking water. Ingestion of trace metal contaminants through drinking water is a probable source of human exposure. Biochemical mechanisms of metallic flavor perception have been previously described; however, less is known about how variations in salivary constituents might impact individuals’ sensitivities to metallic flavors and beverage consumption behaviors. This research presents findings from in vitro experiments, using artificial human saliva, to better understand the role of salivary lipids and proteins on metallic flavor production as measured by biomarkers of metal-induced oxidative stress. The results indicate that metal-induced lipid oxidation, as measured by thiobarbituric acid reactive substances (TBARS), is dominated by salivary proteins, is slightly inhibited in the presence of salivary nitrite, and is detectable by the TBARS method at and above respective concentrations of 9 µM (0.5 mg/L) and 90 µM (5 mg/L), which are both above the aesthetic standards for iron (0.3 mg/L) and copper (1.0 mg/L) in drinking water. Preliminary study with human subjects indicated that reduction in metallic flavor sensitivity, as measured by the best estimate flavor threshold for ferrous iron among 33 healthy adults aged 19–84 years old (22 females), corresponded with reduced drinking water consumption and increased caloric beverage intake among older subjects (>60 years), as determined by a validated self-reported beverage intake questionnaire. These findings provide insights for further research to examine how salivary constituents can impact humans’ sensory abilities in detecting metallic off-flavors in water, and how reduced metallic flavor sensitivity may influence beverage choices and drinking water consumption.
Organophosphorus Pesticide Exposure at 17 Weeks’ Gestation and Odds of Offspring Attention-Deficit/Hyperactivity Disorder Diagnosis in the Norwegian Mother, Father, and Child Cohort Study
Authors: Hall Amber M. , Thistle Jake E. , Manley Cherrel K. , Roell Kyle R. , Ramos Amanda M. , Villanger Gro D. , Reichborn-Kjennerud Ted , Zeiner Pål , Cequier Enrique , Sakhi Amrit K. , Thomsen Cathrine , Aase Heidi , Engel Stephanie M.
Published: December 2022

Prenatal organophosphorus pesticides (OPs) are ubiquitous and have been linked to adverse neurodevelopmental outcomes. However, few studies have examined prenatal OPs in relation to diagnosed attention-deficit/hyperactivity disorder (ADHD), with only two studies exploring this relationship in a population primarily exposed through diet. In this study, we used a nested case-control study to evaluate prenatal OP exposure and ADHD diagnosis in the Norwegian Mother, Father, and Child Cohort Study (MoBa). For births that occurred between 2003 and 2008, ADHD diagnoses were obtained from linkage of MoBa participants with the Norwegian Patient Registry (N = 297), and a reference population was randomly selected from the eligible population (N = 552). Maternal urine samples were collected at 17 weeks’ gestation and molar sums of diethyl phosphates (ΣDEP) and dimethyl phosphates metabolites (ΣDMP) were calculated. Multivariable adjusted logistic regression models were used to estimate the association between prenatal OP metabolite exposure and child ADHD diagnosis. Additionally, multiplicative effect measure modification (EMM) by child sex was assessed. In most cases, mothers in the second and third tertiles of ΣDMP and ΣDEP exposure had slightly lower odds of having a child with ADHD, although confidence intervals were wide and included the null. EMM by child sex was not observed for either ΣDMP or ΣDEP. In summary, we did not find evidence that OPs at 17 weeks’ gestation increased the odds of ADHD in this nested case-control study of ADHD in MoBa, a population primarily experiencing dietary exposure.
Temporal Analysis Reveals the Transient Differential Expression of Transcription Factors That Underlie the Trans-Differentiation of Human Monocytes to Macrophages
Authors: Deng Weihang , Chen Min , Tang Ying , Zhang Le , Xu Zeqian , Li Xinhui , Czajkowsky Daniel M. , Shao Zhifeng
Published: December 2022

The activation of monocytes and their trans-differentiation into macrophages are critical processes of the immune response. Prior work has characterized the differences in the expression between monocytes and macrophages, but the transitional process between these cells is poorly detailed. Here, we analyzed the temporal changes of the transcriptome during trans-differentiation of primary human monocytes into M0 macrophages. We find changes with many transcription factors throughout the process, the vast majority of which exhibit a maximally different expression at the intermediate stages. A few factors, including AP-1, were previously known to play a role in immunological transitions, but most were not. Thus, these findings indicate that this trans-differentiation requires the dynamic expression of many transcription factors not previously discussed in immunology, and provide a foundation for the delineation of the molecular mechanisms associated with healthy or pathological responses that involve this transition.
Gonadal Transcriptome Analysis and Sequence Characterization of Sex-Related Genes in Cranoglanis bouderius
Authors: Wang Dongjie , Pan Zhengkun , Wang Guoxia , Ye Bin , Wang Qiujie , Zuo Zhiheng , Zou Jixing , Xie Shaolin
Published: December 2022

In China, the Cranoglanis bouderius is classified as a national class II-protected animal. The development of C. bouderius populations has been affected by a variety of factors over the past few decades, with severe declines occurring. Considering the likelihood of continued population declines of the C. bouderius in the future, it is critical to investigate the currently unknown characteristics of gonadal differentiation and sex-related genes for C. bouderius conservation. In this study, the Illumina sequencing platform was used to sequence the gonadal transcriptome of the C. bouderius to identify the pathways and genes related to gonadal development and analyze the expression differences in the gonads. A total of 12,002 DEGs were identified, with 7220 being significantly expressed in the ovary and 4782 being significantly expressed in the testis. According to the functional enrichment results, the cell cycle, RNA transport, apoptosis, Wnt signaling pathway, p53 signaling pathway, and prolactin signaling pathway play important roles in sex development in the C. bouderius. Furthermore, the sequence characterization and evolutionary analysis revealed that AMH, DAX1, NANOS1, and AR of the C. bouderius are highly conserved. Specifically, the qRT-PCR results from various tissues showed significant differences in AMH, DAX1, NANOS1, and AR expression levels in the gonads of both sexes of C. bouderius. These analyses indicated that AMH, DAX1, NANOS1, and AR may play important roles in the differentiation and development of C. bouderius gonads. To our best knowledge, this study is the first to analyze the C. bouderius gonadal transcriptome and identify the structures of sex-related genes, laying the foundation for future research.
Real-Time Monitoring of the Cytotoxic and Antimetastatic Properties of Cannabidiol in Human Oral Squamous Cell Carcinoma Cells Using Electric Cell-Substrate Impedance Sensing
Authors: Huang Chien-Chu , Chiu Shao-Chih , Chao Shih-Chi , Liao Heng-Yi , Lee Shiao-Pieng , Huang Chun-Chung , Cho Der-Yang
Published: December 2022

Cannabidiol (CBD) is an active natural compound that is extracted from Cannabis sativa. Previous studies show that CBD is a nonpsychotropic compound with significant anticancer effects. This study determines its cytotoxic effect on oral cancer cells and OEC-M1 cells and compares the outcomes with a chemotherapeutic drug, cisplatin. This study has investigated the effect of CBD on the viability, apoptosis, morphology, and migration of OEC-M1 cells. Electric cell–substrate impedance sensing (ECIS) is used to measure the change in cell impedance for cells that are treated with a series concentration of CBD for 24 h. AlamarBlue and annexin V/7-AAD staining assays show that CBD has a cytotoxic effect on cell viability and induces cell apoptosis. ECIS analysis shows that CBD decreases the overall resistance and morphological parameters at 4 kHz in a concentration-dependent manner. There is a significant reduction in the wound-healing recovery rate for cells that are treated with 30 μM CBD. This study demonstrates that ECIS can be used for in vitro screening of new chemotherapy and is more sensitive, functional, and comprehensive than traditional biochemical assays. CBD also increases cytotoxicity on cell survival and the migration of oral cancer cells, so it may be a therapeutic drug for oral cancer.
Molecular Fingerprint of Human Pathological Synoviocytes in Response to Extractive Sulfated and Biofermentative Unsulfated Chondroitins
Authors: Vassallo Valentina , Stellavato Antonietta , Russo Rosita , Cimini Donatella , Valletta Mariangela , Alfano Alberto , Pedone Paolo Vincenzo , Chambery Angela , Schiraldi Chiara
Published: December 2022

Pharma-grade extractive chondroitin sulfate (CS) is widely used for osteoarthritis (OA) treatment. Recently, unsulfated biofermentative chondroitin (BC) proved positive effects in OA in vitro model. This study, based on primary pathological human synoviocytes, aimed to analyze, by a multiplex assay, a panel of OA-related biomarkers in response to short-term treatments with bovine (CSb), pig (CSp) and fish (CSf) chondroitins, in comparison to BC. As expected, all samples had anti-inflammatory properties, however CSb, CSf and especially BC affected more cytokines and chemokines. Based on these results and molecular weight similarity, CSf and BC were selected to further explore the synoviocytes’ response. In fact, Western blot analyses showed CSf and BC were comparable, downregulating OA-related biomarkers such as the proteins mTOR, NF-kB, PTX-3 and COMP-2. Proteomic analyses, performed by applying a nano-LC-MS/MS TMT isobaric labelling-based approach, displayed the modulation of both common and distinct molecules to chondroitin treatments. Thus, CSf and BC modulated the biological mediators involved in the inflammation cascade, matrix degradation/remodeling, glycosaminoglycans’ synthesis and cellular homeostasis. This study helps in shedding light on different molecular mechanisms related to OA disease that may be potentially affected not only by animal-source chondroitin sulfate but also by unsulfated biofermentative chondroitin.
N-Acetyl Cysteine-Mediated Improvements in Dental Restorative Material Biocompatibility
Authors: Matsuura Takanori , Komatsu Keiji , Ogawa Takahiro
Published: December 2022

The fibroblast-rich gingival tissue is usually in contact with or adjacent to cytotoxic polymer-based dental restoration materials. The objective of this study was to determine whether the antioxidant amino acid, N-acetyl cysteine (NAC), reduces the toxicity of dental restorative materials. Human oral fibroblasts were cultured with bis-acrylic, flowable composite, bulk-fill composite, self-curing acrylic, and titanium alloy test specimens. Cellular behavior and function were analyzed on and around the materials. Impregnation of the bulk-fill composite and self-curing acrylic with NAC reduced their toxicity, improving the attachment, growth, and function of human oral fibroblasts on and around the materials. These mitigating effects were NAC dose dependent. However, NAC impregnation of the bis-acrylic and flowable composite was ineffective, with no cells attaching to nor around the materials. Although supplementing the culture medium with NAC also effectively improved fibroblast behaviors, direct impregnation of materials with NAC was more effective than supplementing the cultures. NAC-mediated improvements in fibroblast behavior were associated with reduced production of reactive oxygen species and oxidized glutathione together with increased glutathione reserves, indicating that NAC effectively directly scavenged ROS from materials and reinforced the cellular antioxidant defense system. These results establish a proof of concept of NAC-mediated improvements in biocompatibility in the selected dental restorative materials.
99mTc-HDP Labeling—A Non-Destructive Method for Real-Time Surveillance of the Osteogenic Differentiation Potential of hMSC during Ongoing Cell Cultures
Authors: Hofmann Jakob , Borcherding Kai , Thiel Karsten , Lingner Thomas , Sommer Ulrike , Haberkorn Uwe , Bewersdorf Tim Niklas , Schmidmaier Gerhard , Grossner Tobias
Published: December 2022

99-Metastabil Technetium (99mTc) is a radiopharmaceutical widely used in skeletal scintigraphy. Recent publications show it can also be used to determine the osteogenic potential of human mesenchymal stem cells (hMSCs) by binding to hydroxyapatite formed during bone tissue engineering. This field lacks non-destructive methods to track live osteogenic differentiation of hMSCs. However, no data about the uptake kinetics of 99mTc and its effect on osteogenesis of hMSCs have been published yet. We therefore evaluated the saturation time of 99mTc by incubating hMSC cultures for different periods, and the saturation concentration by using different amounts of 99mTc activity for incubation. The influence of 99mTc on osteogenic potential of hMSCs was then evaluated by labeling a continuous hMSC culture three times over the course of 3 weeks, and comparing the findings to cultures labeled once. Our findings show that 99mTc saturation time is less than 0.25 h, and saturation concentration is between 750 and 1000 MBq. Repeated exposure to γ-radiation emitted by 99mTc had no negative effects on hMSC cultures. These new insights can be used to make this highly promising method broadly available to support researchers in the field of bone tissue engineering using this method to track and evaluate, in real-time, the osteogenic differentiation of hMSC, without any negative influence on the cell viability, or their osteogenic differentiation potential.
Glioblastoma Molecular Classification Tool Based on mRNA Analysis: From Wet-Lab to Subtype
Authors: Steponaitis Giedrius , Kucinskas Vytautas , Golubickaite Ieva , Skauminas Kestutis , Saudargiene Ausra
Published: December 2022

Most glioblastoma studies incorporate the layer of tumor molecular subtype based on the four-subtype classification system proposed in 2010. Nevertheless, there is no universally recognized and convenient tool for glioblastoma molecular subtyping, and each study applies a different set of markers and/or approaches that cause inconsistencies in data comparability and reproducibility between studies. Thus, this study aimed to create an applicable user-friendly tool for glioblastoma classification, with high accuracy, while using a significantly smaller number of variables. The study incorporated a TCGA microarray, sequencing datasets, and an independent cohort of 56 glioblastomas (LUHS cohort). The models were constructed by applying the Agilent G4502 dataset, and they were tested using the Affymetrix HG-U133a and Illumina Hiseq cohorts, as well as the LUHS cases. Two classification models were constructed by applying a logistic regression classification algorithm, based on the mRNA levels of twenty selected genes. The classifiers were translated to a RT-qPCR assay and validated in an independent cohort of 56 glioblastomas. The classification accuracy of the 20-gene and 5-gene classifiers varied between 90.7–91% and 85.9–87.7%, respectively. With this work, we propose a cost-efficient three-class (classical, mesenchymal, and proneural) tool for glioblastoma molecular classification based on the mRNA analysis of only 5–20 genes, and we provide the basic information for classification performance starting from the wet-lab stage. We hope that the proposed classification tool will enable data comparability between different research groups.
Effect of 1,2-propanediol on the Critical Micelle Concentration of Decyltrimethylammonium Bromide at Temperatures from 293.15 K to 308.15 K
Authors: Romero Carmen M. , Escamilla Andrea P. , Ribeiro Ana C. F. , Esteso Miguel A.
Published: December 2022

It is well known that polar organic compounds, such as alcohols and polyols, exert an appreciable influence on water structure and thus have important effects on surfactant micellization. These substances are often used to modify the properties of surfactants in aqueous solutions, increasing the practical applications they have in diverse industries. In this work, the critical micelle concentration (CMC) of decyltrimethylammonium bromide (C10TAB) in water and in 1,2-propanediol aqueous solutions was determined from both sound velocity and surface tension measurements as a function of surfactant concentration in the temperature range of (293.15 to 308.15) K. The critical micelle concentration of the surfactant increases as the concentration of 1,2-propanediol becomes higher, while the effect on temperature does not show important changes within the range considered. At the selected temperatures, the standard thermodynamic parameters of micellization suggests that the addition of 1,2-propanediol makes the micellization process less favorable. Thermodynamic analysis suggests that the micelle formation of C10TAB is an entropy-driven process at the temperatures considered in this study.
Insights into Manganese Superoxide Dismutase and Human Diseases
Authors: Liu Mengfan , Sun Xueyang , Chen Boya , Dai Rongchen , Xi Zhichao , Xu Hongxi
Published: December 2022

Redox equilibria and the modulation of redox signalling play crucial roles in physiological processes. Overproduction of reactive oxygen species (ROS) disrupts the body’s antioxidant defence, compromising redox homeostasis and increasing oxidative stress, leading to the development of several diseases. Manganese superoxide dismutase (MnSOD) is a principal antioxidant enzyme that protects cells from oxidative damage by converting superoxide anion radicals to hydrogen peroxide and oxygen in mitochondria. Systematic studies have demonstrated that MnSOD plays an indispensable role in multiple diseases. This review focuses on preclinical evidence that describes the mechanisms of MnSOD in diseases accompanied with an imbalanced redox status, including fibrotic diseases, inflammation, diabetes, vascular diseases, neurodegenerative diseases, and cancer. The potential therapeutic effects of MnSOD activators and MnSOD mimetics are also discussed. Targeting this specific superoxide anion radical scavenger may be a clinically beneficial strategy, and understanding the therapeutic role of MnSOD may provide a positive insight into preventing and treating related diseases.
From Basic Radiobiology to Translational Radiotherapy
Authors: Chailapakul Piyawan , Kato Takamitsu A.
Published: December 2022

The Special Issue, entitled “From basic radiobiology to translational radiotherapy”, highlights recent advances in basic radiobiology and the potential to improve radiotherapy in translational research [...]
The Latest Breakthroughs in Immunotherapy for Acute Myeloid Leukemia, with a Special Focus on NKG2D Ligands
Authors: Maurer Stefanie , Zhong Xiaoxuan , Prada Betsy Deza , Mascarenhas John , de Andrade Lucas Ferrari
Published: December 2022

Acute myeloid leukemia (AML) is a hematological malignancy characterized by clonal expansion of stem and myeloid progenitor cells. Immunotherapy has revolutionized the care for other cancers such as solid tumors and lymphomas, and has the potential to effectively treat AML. There has been substantial progress in the developments of immunotherapeutic approaches for AML over the last several years, including the development of antibodies that further increase the innate immunogenicity of leukemia cells by the inhibition of NKG2D ligand—particularly MICA and MICB—shedding, chimeric proteins such as IL-15 superagonist that expand natural killer (NK) cells, blockers of immunologic checkpoints such as NKG2A, and chemicals that indirectly increase expression of immune stimulatory proteins in leukemia stem cells. Furthermore, cellular therapies have been designed to enable alloreactive immunity by allogeneic NK cells or target leukemia antigens such as mutated NPM1. These immunotherapeutic approaches have demonstrated remarkable efficacies in preclinical studies and have successfully transitioned to early phase clinical trials, to establish safety and initial signal of clinical activity. Here, we briefly discuss some of the most recent and impactful developments in the AML immunotherapy field and provide our perspectives for the future directions of this exciting and new therapeutic opportunity.
Iron Restriction Alleviates Atherosclerosis in ApoE KO Mice: An iTRAQ Proteomic Analysis
Authors: Luo Gang , Xiang Lu , Xiao Lin
Published: December 2022

The “iron hypothesis” of atherosclerosis has long been controversial. Several studies have shown that dietary iron restriction or low-iron diets can effectively alleviate atherosclerosis in rabbits and mice. However, the underlying molecular mechanisms of these phenomena remain to be elucidated. In this study, we further evaluated possible correlations between a low-iron diet and atherosclerosis alleviation by using a quantitative proteomic approach. For this purpose, apolipoprotein E knockout (ApoE KO) mice were divided into three groups and fed a normal diet (ND), a high-fat diet (HFD), or a high-fat +low-iron diet (HFD + LI). Our results showed that the HFD-LI improved atherosclerosis by decreasing en face lesions of the aorta and reducing the accumulation of macrophages and disordered smooth muscle cells. HFD-LI also decreased iron levels, serum hepcidin levels and the serum concentration of low-density lipoprotein cholesterol (LDL-C). The use of the isobaric tag for absolute quantification (iTRAQ) proteomic method and subsequent multi-technique molecular validation indicated that many of the proteins involved in atherosclerotic inflammation, vascular remodeling, and focal adhesion had significant changes in their expression among the diet groups. Importantly, the proteins Gal-3 and VCAM1, which are key participants of atherosclerosis pathogenesis, revealed lower expression after a low-iron diet. The present findings widely support the “iron hypothesis” of atherosclerosis. Further studies are suggested to fully understand the implications of these results.
A Novel Tool for the Analysis and Detection of Copy Number Variants Associated with Haemoglobinopathies
Authors: Minaidou Anna , Tamana Stella , Stephanou Coralea , Xenophontos Maria , Harteveld Cornelis L. , Bento Celeste , Kleanthous Marina , Kountouris Petros
Published: December 2022

Several types of haemoglobinopathies are caused by copy number variants (CNVs). While diagnosis is often based on haematological and biochemical parameters, a definitive diagnosis requires molecular DNA analysis. In some cases, the molecular characterisation of large deletions/duplications is challenging and inconclusive and often requires the use of specific diagnostic procedures, such as multiplex ligation-dependent probe amplification (MLPA). Herein, we collected and comprehensively analysed all known CNVs associated with haemoglobinopathies. The dataset of 291 CNVs was retrieved from the IthaGenes database and was further manually annotated to specify genomic locations, breakpoints and MLPA probes relevant for each CNV. We developed IthaCNVs, a publicly available and easy-to-use online tool that can facilitate the diagnosis of rare and diagnostically challenging haemoglobinopathy cases attributed to CNVs. Importantly, it facilitates the filtering of available entries based on the type of breakpoint information, on specific chromosomal and locus positions, on MLPA probes, and on affected gene(s). IthaCNVs brings together manually curated information about CNV genomic locations, functional effects, and information that can facilitate CNV characterisation through MLPA. It can help laboratory staff and clinicians confirm suspected diagnosis of CNVs based on molecular DNA screening and analysis.
Effects of Silver Nanoparticles on Physiological and Proteomic Responses of Tobacco (Nicotiana tabacum) Seedlings Are Coating-Dependent
Authors: Biba Renata , Cvjetko Petra , Tkalec Mirta , Košpić Karla , Štefanić Petra Peharec , Šikić Sandra , Domijan Ana-Marija , Balen Biljana
Published: December 2022

The harmful effects of silver nanoparticles (AgNPs) have been confirmed in many organisms, but the mechanism of their toxicity is not yet fully understood. In biological systems, AgNPs tend to aggregate and dissolve, so they are often stabilized by coatings that influence their physico-chemical properties. In this study, the effects of AgNPs with different coatings [polyvinylpyrrolidone (PVP) and cetyltrimethylammonium bromide (CTAB)] on oxidative stress appearance and proteome changes in tobacco (Nicotiana tabacum) seedlings have been examined. To discriminate between the nanoparticulate Ag form from the ionic one, the treatments with AgNO3, a source of Ag+ ions, were also included. Ag uptake and accumulation were found to be similarly effective upon exposure to all treatment types, although positively charged AgNP-CTAB showed less stability and a generally stronger impact on the investigated parameters in comparison with more stable and negatively charged AgNP-PVP and ionic silver (AgNO3). Both AgNP treatments induced reactive oxygen species (ROS) formation and increased the expression of proteins involved in antioxidant defense, confirming oxidative stress as an important mechanism of AgNP phytotoxicity. However, the mechanism of seedling responses differed depending on the type of AgNP used. The highest AgNP-CTAB concentration and CTAB coating resulted in increased H2O2 content and significant damage to lipids, proteins and DNA molecules, as well as a strong activation of antioxidant enzymes, especially CAT and APX. On the other hand, AgNP-PVP and AgNO3 treatments induced the nonenzymatic antioxidants by significantly increasing the proline and GSH content. Exposure to AgNP-CTAB also resulted in more noticeable changes in the expression of proteins belonging to the defense and stress response, carbohydrate and energy metabolism and storage protein categories in comparison to AgNP-PVP and AgNO3. Cysteine addition significantly reduced the effects of AgNP-PVP and AgNO3 for the majority of investigated parameters, indicating that AgNP-PVP toxicity mostly derives from released Ag+ ions. AgNP-CTAB effects, however, were not alleviated by cysteine addition, suggesting that their toxicity derives from the intrinsic properties of the nanoparticles and the coating itself.
Role of Bioactive Molecules on Neuroprotection, Oxidative Stress, and Neuroinflammation Modulation
Authors: Di Liberto Valentina , Mudò Giuseppa
Published: December 2022

As the global population ages, the burden of neurodegenerative and neurological disorders is dramatically increasing [...]
Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents
Authors: Żmudzka Elżbieta , Lustyk Klaudia , Głuch-Lutwin Monika , Mordyl Barbara , Zakrzewska-Sito Alicja , Mierzejewski Paweł , Jaśkowska Jolanta , Kołaczkowski Marcin , Sapa Jacek , Pytka Karolina
Published: December 2022

Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound’s intrinsic activity towards dopamine D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors. However, the effect on the 5-HT2A and 5-HT7 receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide.
The Impact of Cytokines in Coronary Atherosclerotic Plaque: Current Therapeutic Approaches
Authors: Tsioufis Panagiotis , Theofilis Panagiotis , Tsioufis Konstantinos , Tousoulis Dimitris
Published: December 2022

Coronary atherosclerosis is a chronic pathological process that involves inflammation together with endothelial dysfunction and lipoprotein dysregulation. Experimental studies during the past decades have established the role of inflammatory cytokines in coronary artery disease, namely interleukins (ILs), tumor necrosis factor (TNF)-α, interferon-γ, and chemokines. Moreover, their value as biomarkers in disease development and progression further enhance the validity of this interaction. Recently, cytokine-targeted treatment approaches have emerged as potential tools in the management of atherosclerotic disease. IL-1β, based on the results of the CANTOS trial, remains the most validated option in reducing the residual cardiovascular risk. Along the same line, colchicine was also proven efficacious in preventing major adverse cardiovascular events in large clinical trials of patients with acute and chronic coronary syndrome. Other commercially available agents targeting IL-6 (tocilizumab), TNF-α (etanercept, adalimumab, infliximab), or IL-1 receptor antagonist (anakinra) have mostly been assessed in the setting of other inflammatory diseases and further testing in atherosclerosis is required. In the future, potential targeting of the NLRP3 inflammasome, anti-inflammatory IL-10, or atherogenic chemokines could represent appealing options, provided that patient safety is proven to be of no concern.
Specific S100 Proteins Bind Tumor Necrosis Factor and Inhibit Its Activity
Authors: Kazakov Alexey S. , Zemskova Marina Y. , Rystsov Gleb K. , Vologzhannikova Alisa A. , Deryusheva Evgenia I. , Rastrygina Victoria A. , Sokolov Andrey S. , Permyakova Maria E. , Litus Ekaterina A. , Uversky Vladimir N. , Permyakov Eugene A. , Permyakov Sergei E.
Published: December 2022

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The apparent Kd values for the complexes of multimeric sTNF with S100A11/A12 estimated from fluorimetric titrations are 0.1–0.3 µM. S100A12/A13 suppress the cytotoxic activity of sTNF against Huh-7 cells, as evidenced by the MTT assay. Structural modeling indicates that the sTNF-S100 interactions may interfere with the sTNF recognition by the therapeutic anti-TNFs. Bioinformatics analysis reveals dysregulation of TNF and S100A11/A12/A13 in numerous disorders. Overall, we have shown a novel potential regulatory role of the extracellular forms of specific S100 proteins that may affect the efficacy of anti-TNF treatment in various diseases.
Increased Intestinal Permeability and Stool Zonulin, Calprotectin and Beta-Defensin-2 Concentrations in Allogenic Hematopoietic Cell Transplantation Recipients
Authors: Tyszka Martyna , Maciejewska-Markiewicz Dominika , Biliński Jarosław , Lubas Arkadiusz , Stachowska Ewa , Basak Grzegorz W.
Published: December 2022

Significant progress has been made in understanding the connection between intestinal barrier function and allogenic hematopoietic cell transplantation (allo-HCT) recipients’ outcomes. The purpose of this study was to further evaluate gut barrier permeability and other potential intestinal barrier disruption markers in the allo-HCT setting. Fifty-one patients were enrolled in the study. Intestinal permeability was assessed with the sugar absorption test and faecal concentrations of the zonulin, calprotectin and beta-defensin-2 levels in the peri-transplantation period. Most patients undergoing allo-HCT in our department had a disrupted intestinal barrier at the baseline, which was associated with older age and higher Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Regardless of this, we observed a further increase in gut barrier permeability after allo-HCT in most patients. However, there was no association between permeability assay and other markers (zonulin, calprotectin and beta-defensin-2). Patients with acute GVHD had significantly higher median calprotectin concentrations after allo-HCT compared with the patients without this complication. Our findings indicate that gut barrier damage develops prior to allo-HCT with progression after the procedure and precedes further complications, but did not prove other markers to be useful surrogates of intestinal permeability.
Method of the Mechanical Properties Evaluation of Polyethylene Gas Pipelines with Portable Hardness Testers
Authors: Vinogradova Anna , Gogolinskii Kirill , Umanskii Alexander , Alekhnovich Varvara , Tarasova Alena , Melnikova Alena
Published: December 2022

This article is devoted to the study of means and methods for non-destructive testing mechanical properties of polyethylene gas pipelines that have been in operation for 25–55 years. In order to assess mechanical properties, stress at yield was chosen as a key parameter. Stress at yield is determined from the results of tensile tests and is associated with the limiting circumferential (hoop) stress, determined from the results of tests for short-term pressure. Tensile tests require sample cutting and the shutdown of pipelines’ service. To solve this problem of nondestructive testing of pipelines, tests were carried out using the methods of Shore, Leeb and dynamic instrumental indentation. According to the test results, it was revealed that the correlation coefficient between the values of stress at yield and hardness, obtained by the method of dynamic instrumental indentation, is 0.98 which confirms the possibility of the evaluation of the mechanical properties of pipelines by the method of dynamic instrumental indentation.
Molecular Mechanism Underlying Role of the XBP1s in Cardiovascular Diseases
Authors: Liu Shu , Ding Hong , Li Yongnan , Zhang Xiaowei
Published: December 2022

Spliced X-box binding protein-1 (XBP1s) is a protein that belongs to the cAMP-response element-binding (CREB)/activating transcription factor (ATF) b-ZIP family with a basic-region leucine zipper (bZIP). There is mounting evidence to suggest that XBP1s performs a critical function in a range of different cardiovascular diseases (CVDs), indicating that it is necessary to gain a comprehensive knowledge of the processes involved in XBP1s in various disorders to make progress in research and clinical therapy. In this research, we provide a summary of the functions that XBP1s performs in the onset and advancement of CVDs such as atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. Furthermore, we discuss XBP1s as a novel therapeutic target for CVDs.