bluuebunny/crossref_metadata_2025 huggingface dataset:
Mindfulness and Relaxation Techniques for Stroke Survivors with Aphasia: A Feasibility and Acceptability Study
Authors: Wang Xu , Thiel Lindsey , Graff Naomi de
Published: July 2022

Stroke survivors with aphasia (SsWA) tend to experience high levels of anxiety and stress, leading to an increased risk of recurrent strokes. Mindfulness and/or relaxation that does not require language outputs could reduce psychosocial stress; however, these approaches work best if they consist of a range of techniques and are modified to suit the needs of SsWA. Using a mixed-methods approach, we examined the feasibility and acceptability of a set of tailored mindfulness and relaxation techniques for SsWA. Nine SsWA were recruited (six men and three women, median age = 51 years). Four relaxation and mindfulness techniques which had been tailored for SsWA were filmed into a DVD/YouTube video and were given to participants together with a practice diary for home practice once daily for 5 weeks. The participants joined focus group discussions and completed a feasibility scale 5 weeks later. The participants perceived these techniques as easy, user-friendly and acceptable for SsWA in general. Although practised less often than instructed, many participants reported benefits of regular practice. The perceived relevance of these techniques to the participants’ own situations and the intention to continue varied. Future research could encourage the regular practice of self-help interventions by incorporating behavioural change techniques such as using prompts and cues.
Influence of 2iP and 2,4-D Concentrations on Accumulation of Biomass, Phenolics, Flavonoids and Radical Scavenging Activity in Date Palm (Phoenix dactylifera L.) Cell Suspension Culture
Authors: Al-Khayri Jameel Mohammed , Naik Poornananda Madhava
Published: July 2022

Plant hormones are chemical compounds that serve as crucial signal molecules. The growth and induction of bioactive compounds in plant suspension cultures depend on the exogenous application of auxins and cytokinins at different concentrations. In this study, date palm (Phoenix dactylifera L., cv. Shishi) cell suspension cultures initiated in Murashige and Skoog (MS) medium were treated with 2.5 and 5 mg/L 2-isopentenyladenine (2-iP) in combinations with 1, 2.5, 5 and 10 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), and compared to the standard cell multiplication medium as the control, which contained 1.5 mg/L 2iP and 10 mg/L naphthaleneacetic acid (NAA). The optimum biomass accumulation, based on the packed cell volume and dry weight, was found in the cell suspension culture augmented with 1 mg/L 2,4-D + 5 mg/L 2iP followed by 5 mg/L 2,4-D + 2.5 mg/L 2-iP. In addition, the study assessed the total phenolic, flavonoid and radical scavenging activity, and high performance liquid chromatography (HPLC) was also used to determine the content of polyphenols (apigenin, caffeic acid, catechin and kaempferol) quantitatively. Cell suspension cultures containing 5 mg/L 2,4-D and 2.5 mg/L 2iP yielded the maximum accumulation of phenolics, flavonoids and radical scavenging activity (90.65%), and also a significantly higher content of caffeic acid (37.1 µg/g DW). The present finding facilitates the scaling up and commercial production of polyphenols from date palm cell suspension culture.
Traditional Herbal Medicine as a Tool to Explore New Frontiers in Pharmacology
Authors: Motti Riccardo
Published: July 2022

The aim of this Special Issue, entitled “Botany, Phytochemistry and Pharmacology in Traditional Herbal Medicine”, was to expand our knowledge about natural products of plant origin that are largely used in traditional phytotherapy [...]
Methods for Characterizing Groundwater Resources with Sparse In Situ Data
Authors: Nishimura Ren , Jones Norman L. , Williams Gustavious P. , Ames Daniel P. , Mamane Bako , Begou Jamila
Published: July 2022

Accurate characterization of groundwater resources is required for sustainable management. Due to the cost of installing monitoring wells and challenges in collecting and managing in situ data, groundwater data are sparse—especially in developing countries. In this study, we demonstrate an analysis of long-term groundwater storage changes using temporally sparse but spatially dense well data, where each well had as few as one historical groundwater measurement. We developed methods to synthetically estimate groundwater table elevation (WTE) times series by clustering wells using two different methods; a uniform grid and k-means-constrained clustering to create pseudo-wells. These pseudo-wells had a more complete groundwater level time history, which we then temporally and spatially interpolated to analyze groundwater storage changes in an aquifer. We demonstrated these methods on the Beryl-Enterprise aquifer in Utah, USA, where other researchers quantified the groundwater storage depletion rate, and the wells had a large number of historical measurements. We randomly used one measurement per well and showed that our methods yielded storage depletion rates similar to published values. We applied the method to a region in southern Niger where wells had only one measurement per well, and showed that our estimated groundwater storage change trend reasonably matched that which was calculated using GRACE satellite data.
The Effect of Expertise during Simulated Flight Emergencies on the Autonomic Response and Operative Performance in Military Pilots
Authors: Santos Sara , Parraca Jose , Fernandes Orlando , Villafaina Santos , Clemente-Suarez Vicente , Melo Filipe
Published: July 2022

Heart rate variability (HRV) and performance response during emergency flight maneuvers were analyzed. Two expert pilots (ages 35 and 33) and two rookie pilots (ages 25) from the Portuguese Air Force participated in this case–control report study. Participants had to complete the following emergency protocols in a flight simulator: (1) take-off engine failure, (2) flight engine failure close to the base, (3) flight engine failure far away from the base, and (4) alternator failure. The HRV was collected during all these maneuvers, as well as the performance data (the time it took to go through the emergency protocol and the subjective information from the flight simulator operator). Results regarding autonomic modulation showed a higher sympathetic response during the emergency maneuvers when compared to baseline. In some cases, there was also a higher sympathetic response during the emergency maneuvers when compared with the take-off protocol. Regarding performance data, the expert pilots accomplished the missions in less time than the rookie pilots. Autonomic modulation measured from HRV through portable devices can easily relay important information. This information is relevant since characterizing these maneuvers can provide helpful information to design training strategies to improve those psychophysiological responses.
Insights into the Antimicrobial Resistance Profile of a Next Generation Probiotic Akkermansia muciniphila DSM 22959
Authors: Machado Daniela , Barbosa Joana Cristina , Almeida Diana , Andrade José Carlos , Freitas Ana Cristina , Gomes Ana Maria
Published: July 2022

Akkermansia muciniphila is a Gram-negative intestinal anaerobic bacterium recently proposed as a novel probiotic candidate to be incorporated in food and pharmaceutical forms. Despite its multiple health benefits, the data addressing its antimicrobial susceptibility profile remain scarce. However, the absence of acquired resistance in probiotic strains is a compulsory criterion for its approval in the qualified presumption of safety list. This study aimed at characterizing the A. muciniphila DSM 22959 strain’s antimicrobial susceptibility profile using phenotypic and in silico approaches. To establish the phenotypic antimicrobial susceptibility profile of this strain, minimum inhibitory concentrations of eight antimicrobials were determined using broth microdilution and E-test methods. Additionally, the A. muciniphila DSM 22959 genome was screened using available databases and bioinformatics tools to identify putative antimicrobial resistance genes (ARG), virulence factors (VF), genomic islands (GI), and mobile genetic elements (MGE). The same categorization was obtained for both phenotypic methods. Resistance phenotype was observed for gentamicin, kanamycin, streptomycin, and ciprofloxacin, which was supported by the genomic context. No evidence was found of horizontal acquisition or potential transferability of the identified ARG and VF. Thus, this study provides new insights regarding the phenotypic and genotypic antimicrobial susceptibility profiles of the probiotic candidate A. muciniphila DSM 22959.
Examining Perceived Stress and Coping Strategies of University Students during COVID-19: A Cross-Sectional Study in Jordan
Authors: Alduais Fahd , Samara Abeer Ihsan , Al-Jalabneh Heba Mustafa , Alduais Ahmed , Alfadda Hind , Alaudan Rasha
Published: July 2022

COVID-19 has changed our lives in all arenas, including higher education and psychological well-being. Three objectives were set forth in this study. We started by examining issues related to online education during the pandemic in Jordan, particularly for students pursuing business studies. Second, we assessed academic, behavioural, and financial stressors that business students experience at Jordanian higher education institutions. Lastly, we examined the possible coping methods students employed to cope and adapt during the pandemic. A descriptive cross-sectional study was conducted based on the perceived stress scale distributed to 473 Jordanian undergraduate students (18–27 years of age), across both public and private universities. Results showed an association between academic, behavioural, and financial stressors and students’ perceived stress. While students perceived various levels and types of stress during COVID-19, including academic, behavioural, and financial, they also experienced new online skills. However, despite coping with stress, some students (especially females) displayed more stress because of the deficient course content, which added to their perceived stress and left them feeling unmotivated. This study contributes to bettering the university students’ mental health.
Anxiety Disorder and Smoking Behavior: The Moderating Effects of Entertainment and Informational Television Viewing
Authors: Hwang Juwon , Borah Porismita
Published: July 2022

Smoking is more common among individuals with mental health issues than those who do not have mental illnesses. In particular, among individuals with an anxiety disorder, a high prevalence of smoking has been found. Mood adjustment theory suggests that individuals with negative moods could adjust their moods depending on the type of television they watched. To understand this relationship better, we aim to examine how different television viewing can moderate the tendency of smoking behavior for individuals with an anxiety disorder. We used national U.S. survey data and concepts from the mood adjustment theory to answer our research questions. Our main contributions were to: (1) extend the mood adjustment theory by focusing on the association between a diagnosed mental disorder (i.e., anxiety) and risky behavior (i.e., smoking), and (2) examine the nuances of television genres by dividing entertainment television into excitement-valenced and ambiguously-valenced entertainment programs, along with information programs. The primary findings show that individuals with an anxiety disorder were more likely to smoke and this association was significantly attenuated when they watched cartoons, sports, and health information programs, but the positive association between an anxiety disorder and the extent of smoking was intensified when they watched drama, music, sci-fi, and television news. Patients with an anxiety disorder may take advantage of excitement-valenced entertainment programs and health-related information but need to be cautious in choosing ambiguously-valenced entertainment programs and news.
The Impact of Effective Communication on Perceptions of Patient Safety—A Prospective Study in Selected Polish Hospitals
Authors: Kulińska Janina , Rypicz Łukasz , Zatońska Katarzyna
Published: July 2022

Interpersonal communication plays a key role in the treatment process. It affects not only the patient’s satisfaction with the course of treatment, but also allows the achievement of the best outcome in the therapeutic process. The process of patient empowerment and putting them in the role of a partner in the therapeutic process makes it possible to build a relationship based on trust, kindness and empathy. The aim of the study is to show the relationship between a patient’s sense of safety and access to health information, friendly and empathetic treatment by medical staff and a relationship based on trust. The study is conducted on patients from public hospitals in Wrocław by using the author’s questionnaire. One of the five most important factors according to respondents is the sense of safety, as reported by more than half of the patients (54.4%)—this is the opinion of more than half of the patients (54.4%). The respondents assessed the quality of patient care as an average of M = 41.1/50 points. There is a strong positive correlation between the sense of security and the access to information (rho = 0.642), kind treatment (rho = 0.623), trust in medical staff (rho = 0.758) and satisfaction with hospital stay (rho = 0.758).
The Impact of the COVID-19 Pandemic on the Orthopedic Residents: A Pan-Romanian Survey
Authors: Moldovan Flaviu , Gligor Adrian , Moldovan Liviu , Bataga Tiberiu
Published: July 2022

The COVID-19 pandemic has brought unprecedented challenges, with a potential stress which might affect the education of resident doctors in the field of orthopedics and traumatology. Its repercussion on the residents’ strain and training routes is not well known. After two years of pandemic, this paper aims to analyze the repercussion of the coronavirus disease 2019 (COVID-19) on education, medical training, and the mental well-being of Romanian resident doctors in orthopedics and traumatology. In January–February 2022, an electronic questionnaire was distributed to all orthopedic resident doctors in the 12 residential training centers in Romania. Participants (n = 236) were resident doctors with an employment contract and professional activity during the COVID-19 pandemic. Resident doctors who did not work during this period were excluded. An online survey generator was used to electronically create the questionnaire. Statistical analysis was performed in Matlab version R2022a, with the support of Statistics and Machine Learning Toolbox Version 12.3. Descriptive statistics were performed for the standardized questions, while for the open questions, answers were collected by topic. The results of the Chi-square test indicate that there is a statistically significant association regarding the prevalence of infection among residents involved in the treatment of patients with COVID-19 (p = 0.028), and the influence of secondment in COVID-19 sections (p = 0.0003). The infection of residents is not related to their affiliation with a particular medical training center (p = 0.608), gender (p = 0.175), the year of study in residency (p = 0.733), the age group (p = 0.178), and the secondment period (p = 0.114). Residents who participated in the study had an overall well-being index of 13.8 ± 5.7, which indicates a low level of well-being for a large number of residents. Residents who would like to choose a new residency specialization, or would choose a non-medical career, had reduced average WHO wellness rates, as the risk of infection is associated with the treatment of patients with COVID-19 and secondment in COVID-19 sections. The findings of this study may help residency training centers to develop robust programs that can alleviate the impact of this pandemic. Some major changes will be needed to be integrated into residency training programs around the world. Emphasis should be placed on electronic educational portfolios, simulation of surgical processes, and distance learning, all of which have a high potential for health and safety, as well as for the moral support of residents.
Receiver Operating Characteristic Curve Analysis of the Somatosensory Organization Test, Berg Balance Scale, and Fall Efficacy Scale–International for Predicting Falls in Discharged Stroke Patients
Authors: Fiedorová Iva , Mrázková Eva , Zádrapová Mariana , Tomášková Hana
Published: July 2022

Background: Although fall prevention in patients after stroke is crucial, the clinical validity of fall risk assessment tools is underresearched in this population. The study aim was to determine the cut-off scores and clinical validity of the Sensory Organization Test (SOT), the Berg Balance Scale (BBS), and the Fall Efficacy Scale–International (FES-I) in patients after stroke. Methods: In this prospective cross-sectional study, we analyzed data for patients admitted to a rehabilitation unit after stroke from 2018 through 2021. Participants underwent SOT, BBS, and FES-I pre-discharge, and the fall incidence was recorded for 6 months. We used an area under the receiver operating characteristic curve (AUC) to calculate predictive values. Results: Of 84 included patients (median age 68.5 (interquartile range 67–71) years), 32 (38.1%) suffered a fall. All three tests were significantly predictive of fall risk. Optimal cut-off scores were 60 points for SOT (AUC 0.686), 35 and 42 points for BBS (AUC 0.661 and 0.618, respectively), and 27 and 29 points for FES-I (AUC 0.685 and 0.677, respectively). Conclusions: Optimal cut-off scores for SOT, BBS, and FES-I were determined for patients at risk for falls after a stroke, which all three tools classified with a good discriminatory ability.
Local Disproportions of Quality of Life and Their Influence on the Process of Green Economy Development in Polish Voivodships in 2010–2020
Authors: Drozdowski Grzegorz , Dziekański Paweł
Published: July 2022

Voivodships are centres of economic, social, and cultural life—they gather economic and social activities. This research aimed to evaluate the spatial differentiation of the quality of life in voivodships in Poland with the use of a synthetic measure. To achieve the research objective, the research methods used were literature analysis, statistical analysis, and synthetic measure. The Technique for Order Preference by Similarity to an Ideal Solution method was used to build synthetic measures. The choice of variables in 2010–2020 was largely conditioned by the availability of data collected in the regional system at the level of voivodships at the Local Data Bank of the Central Statistical Office. As a result of the analysis of voivodships in Poland, based on the quality of life measure, four groups were distinguished (according to the value of quartiles). In the group of the best voivodeships there were: Pomerania, Masovia, Lower Silesia, and West Pomeranian in 2010, and Masovia, Pomerania, Greater Poland, Lower Silesia, and Lesser Poland in 2020, and in the IV, the weakest group: Lodz Province, Podlasie Province, Lubusz Province, and Holy Cross in 2010, and Lodz Province, Podlasie Province, Holy Cross, and Lublin Province in 2020. The synthetic quality of life ranged from 0.37 to 0.56 in 2010 and from 0.39 to 0.64 in 2020. Regional authorities, taking care to improve economic potential, cause increasing the attractiveness of the area and attracting new entrepreneurs, create new jobs, and improve the quality of life of the inhabitants. Quality of life is shaped by economic activity and working conditions, health, education, free time and social relations, economic and physical security, and the quality of the natural environment. The results of the research conducted allow local governments to make comparisons. The conclusions drawn may allow them to identify potential directions for developing policy optimization.
Does the National Fitness Policy Promote National Health?—An Empirical Study from China
Authors: Zheng Jun-Yi , Luan Li-Xia , Sun Mei
Published: July 2022

The influence of national health level in the stability and sustainable development of national society is increasingly prominent. The purpose of this study is to examine whether, when, and how national fitness policies exert influence on national health. Panel data from 2008 to 2017 of 30 Chinese provinces (cities) (except the Tibet autonomous region) were used to systematically reveal the direct impact of national fitness policies on national health and its characteristics in different regions, as well as the interaction mechanisms of human capital and finance health expenditures in public sports. This study found that first, national fitness policies had a positive effect on adult health. Second, sports human capital weakens the health effect of national fitness policies, while public finance health expenditures strengthen this effect. Lastly, the health effect of national fitness policies varies significantly across regions due to uneven regional economic development, and the differences in the effects on different age groups (adults and children) are equally pronounced. This study suggests that national fitness public service system and diverse national fitness plans improving national health level are important for a new dynamic balance and high quality coordinated development in both Chinese economic growth and social welfare.
Classifying Young Children with Attention-Deficit/Hyperactivity Disorder Based on Child, Parent, and Family Characteristics: A Cross-Validation Study
Authors: Law Evelyn , Sideridis Georgios , Alkhadim Ghadah , Snyder Jenna , Sheridan Margaret
Published: July 2022

We aimed to identify subgroups of young children with differential risks for ADHD, and cross-validate these subgroups with an independent sample of children. All children in Study 1 (N = 120) underwent psychological assessments and were diagnosed with ADHD before age 7. Latent class analysis (LCA) classified children into risk subgroups. Study 2 (N = 168) included an independent sample of children under age 7. A predictive model from Study 1 was applied to Study 2. The latent class analyses in Study 1 indicated preference of a 3-class solution (BIC = 3807.70, p < 0.001). Maternal education, income-to-needs ratio, and family history of psychopathology, defined class membership more strongly than child factors. An almost identical LCA structure from Study 1 was replicated in Study 2 (BIC = 5108.01, p < 0.001). Indices of sensitivity (0.913, 95% C.I. 0.814–0.964) and specificity (0.788, 95% C.I. 0.692–0.861) were high across studies. It is concluded that the classifications represent valid combinations of child, parent, and family characteristics that are predictive of ADHD in young children.
Influence of Menstrual Cycle on Leukocyte Response Following Exercise-Induced Muscle Damage
Authors: Funaki Akiko , Gam Hyunjun , Matsuda Tomoka , Ishikawa Akira , Yamada Mizuki , Ikegami Nodoka , Nishikawa Yuriko , Sakamaki-Sunaga Mikako
Published: July 2022

We investigated the influence of the menstrual cycle (MC) on leukocyte response after exercise-induced muscle damage (EIMD). During the early follicular (E-FP, n = 12) or mid-luteal phase (M-LP, n = 12), 24 untrained females with eumenorrhea performed 60 eccentric exercises using nondominant arms. Blood samples were collected at pre- and 4, 48, and 96 h postexercise to analyze estradiol and progesterone concentrations, leukocyte count and fractionation, and creatine kinase (CK) activity. We also assessed the maximal voluntary isometric contraction torque of elbow flexion, range of motion in the elbow joint, upper-arm circumference, and muscle soreness as indirect muscle damage markers at pre-; immediately post-; and 4, 48, and 96 h postexercise. The percent change in neutrophil counts from pre- to 4 h postexercise was lower in M-LP than in E-FP (E-FP, 30.7% [15.9–65.7%] vs. M-LP, 10.3% [−2.3–30.0%]; median [interquartile range: 25–75%]; p = 0.068). Progesterone concentration at pre-exercise was significantly negatively correlated with the percent change in neutrophil counts from pre- to 4 h postexercise in M-LP (r = −0.650, p = 0.022). MC did not affect CK activity or other muscle damage markers. Thus, progesterone concentration rather than MC may be related to neutrophil response following EIMD.
Parental Attributions—Mothers’ Voices in Economically and Socially Disadvantaged Contexts
Authors: Narciso Isabel , Albuquerque Sara , Ribeiro Maria Francisca , Ferreira Luana Cunha , Fernandes Mariana
Published: July 2022

In the present study, the attributions of socially and economically disadvantaged mothers for their own negative parenting behavior and for their children’s undesirable behaviors as perceived by parents—understood as misbehavior—were analyzed. To this end, an exploratory study with a qualitative design was developed, in which 24 socially and economically disadvantaged mothers were individually interviewed. The data were analyzed following a thematic analysis approach, using software suited to qualitative analysis, namely NVIVO 12. The children’s undesirable behaviors as perceived by parents and some characteristics associated with parental performance (particularly the appraisal of the effectiveness of their negative practices) emerged respectively as external and internal factors, explaining mothers’ inadaptive behaviors—difficulties in behavior regulation, physical coercion, psychological control and paraverbal hostility. The parental subsystem and school emerged as the main external factors, and the psychological characteristics as the most relevant internal factors, explaining the children’s undesirable behaviors—challenge, immaturity, hostility, emotionally-based, school behavior/absenteeism and danger. The results also indicate weak self-critical reflexivity regarding some of the inadaptive behaviors. The comprehensive analysis of the results, based on the literature review, gave rise to an explanatory hypothesis on the dysfunctional circular process regarding the maintenance of inadaptive practices and children’s undesirable behaviors, considering the role played by parental attributions and by insufficient parental reflexivity.
Role of Glycolysis/Gluconeogenesis and HIF-1 Signaling Pathways in Rats with Dental Fluorosis Integrated Proteomics and Metabolomics Analysis
Authors: Ba Yue , Yang Shuo , Yu Shuiyuan , Hou Xiangbo , Du Yuhui , Gao Minghui , Zuo Juan , Sun Lei , Fu Xiaoli , Li Zhiyuan , Huang Hui , Zhou Guoyu , Yu Fangfang
Published: July 2022

Fluoride is widely distributed, and excessive intake will lead to dental fluorosis. In this study, six offspring rats administrated 100 mg/L sodium fluoride were defined as the dental fluorosis group, and eight offspring rats who received pure water were defined as the control group. Differentially expressed proteins and metabolites extracted from peripheral blood were identified using the liquid chromatography tandem mass spectrometry and gas chromatography mass spectrometry, with the judgment criteria of fold change >1.2 or <0.83 and p < 0.05. A coexpression enrichment analysis using OmicsBean was conducted on the identified proteins and metabolites, and a false discovery rate (FDR) < 0.05 was considered significant. Human Protein Atlas was used to determine the subcellular distribution of hub proteins. The Gene Cards was used to verify results. A total of 123 up-regulated and 46 down-regulated proteins, and 12 up-regulated and 2 down-regulated metabolites were identified. The significant coexpression pathways were the HIF-1 (FDR = 1.86 × 10−3) and glycolysis/gluconeogenesis (FDR = 1.14 × 10−10). The results of validation analysis showed the proteins related to fluorine were mainly enriched in the cytoplasm and extrinsic component of the cytoplasmic side of the plasma membrane. The HIF-1 pathway (FDR = 1.01 × 10−7) was also identified. Therefore, the HIF-1 and glycolysis/gluconeogenesis pathways were significantly correlated with dental fluorosis.
The Role of Platelets in Diabetic Kidney Disease
Authors: Rustiasari Ukhti Jamil , Roelofs Joris J.
Published: July 2022

Diabetic kidney disease (DKD) is among the most common microvascular complications in patients with diabetes, and it currently accounts for the majority of end-stage kidney disease cases worldwide. The pathogenesis of DKD is complex and multifactorial, including systemic and intra-renal inflammatory and coagulation processes. Activated platelets play a pivotal role in inflammation, coagulation, and fibrosis. Mounting evidence shows that platelets play a role in the pathogenesis and progression of DKD. The potentially beneficial effects of antiplatelet agents in preventing progression of DKD has been studied in animal models and clinical trials. This review summarizes the current knowledge on the role of platelets in DKD, including the potential therapeutic effects of antiplatelet therapies.
Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog
Authors: González-Berdullas Patricia , Pereira Renato B. , Teixeira Cláudia , Silva José Pedro , Magalhães Carla M. , Rodríguez-Borges José E. , Pereira David M. , Esteves da Silva Joaquim C. G. , Pinto da Silva Luís
Published: July 2022

Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the bioluminescent system of marine Coelenterazine: Coelenterazine (Clz) itself, Coelenteramide (Clmd), and Coelenteramine (Clm). We have found that Clz derivatives possess variable anticancer activity toward gastric and lung cancer. Interestingly, we also found that both brominated Clmd (Br-Clmd) and Clm (Br-Clm) were the most potent anticancer compounds toward these cell lines, with this being the first report of the anticancer potential of these types of molecules. Interestingly, Br-Clm possessed some safety profile towards noncancer cells. Further evaluation revealed that the latter compound induced cell death via apoptosis, with evidence for crosstalk between intrinsic and extrinsic pathways. Finally, a thorough exploration of the chemical space of the studied Br-Clm helped identify the structural features responsible for its observed anticancer activity. In conclusion, a new type of compounds with anticancer activity toward gastric and lung cancer was reported and characterized, which showed interesting properties to be considered as a starting point for future optimizations towards obtaining suitable chemotherapeutic agents.
Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain
Authors: Ren Jinxuan , Lin Jiaqi , Yu Lina , Yan Min
Published: July 2022

The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.
Using Genomic Selection to Develop Performance-Based Restoration Plant Materials
Authors: Jones Thomas A. , Monaco Thomas A. , Larson Steven R. , Hamerlynck Erik P. , Crain Jared L.
Published: July 2022

Effective native plant materials are critical to restoring the structure and function of extensively modified ecosystems, such as the sagebrush steppe of North America’s Intermountain West. The reestablishment of native bunchgrasses, e.g., bluebunch wheatgrass (Pseudoroegneria spicata [Pursh] À. Löve), is the first step for recovery from invasive species and frequent wildfire and towards greater ecosystem resiliency. Effective native plant material exhibits functional traits that confer ecological fitness, phenotypic plasticity that enables adaptation to the local environment, and genetic variation that facilitates rapid evolution to local conditions, i.e., local adaptation. Here we illustrate a multi-disciplinary approach based on genomic selection to develop plant materials that address environmental issues that constrain local populations in altered ecosystems. Based on DNA sequence, genomic selection allows rapid screening of large numbers of seedlings, even for traits expressed only in more mature plants. Plants are genotyped and phenotyped in a training population to develop a genome model for the desired phenotype. Populations with modified phenotypes can be used to identify plant syndromes and test basic hypotheses regarding relationships of traits to adaptation and to one another. The effectiveness of genomic selection in crop and livestock breeding suggests this approach has tremendous potential for improving restoration outcomes for species such as bluebunch wheatgrass.
Does G Protein-Coupled Estrogen Receptor 1 Contribute to Cisplatin-Induced Acute Kidney Injury in Male Mice?
Authors: Gohar Eman Y. , Almutlaq Rawan N. , Fan Chunlan , Balkawade Rohan S. , Butt Maryam K. , Curtis Lisa M.
Published: July 2022

Nephrotoxicity is the dose-limiting side-effect of the chemotherapeutic agent cisplatin (Cp). Recent evidence points to renal protective actions of G protein-coupled estrogen receptor 1 (GPER1). In addition, it has been shown that GPER1 signaling elicits protective actions against acute ischemic injuries that involve multiple organ systems; however, the involvement of GPER1 signaling in Cp-induced acute kidney injury (AKI) remains unclear. This study tested whether genetic deletion of GPER1 exacerbates Cp-induced AKI in male mice. We subjected male mice, homozygous (homo) and heterozygous (het) knockout for the GPER1 gene, and wild-type (WT) littermates to Cp or saline injections and assessed markers for renal injury on the third day after injections. We also determined serum levels of proinflammatory markers in saline and Cp-treated mice. Given the protective role of heme oxygenase-1 (HO-1) in Cp-mediated apoptosis, we also investigated genotypic differences in renal HO-1 abundance, cell death, and proliferation by Western blotting, the TUNEL assay, and Ki67 immunostaining, respectively. Cp increased serum creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL) levels, the renal abundance of kidney injury molecule-1, and NGAL in all groups. Cp-induced AKI resulted in comparable histological evidence of injury in all genotypes. WT and homo mice showed greater renal HO-1 abundance in response to Cp. Renal HO-1 abundance was lower in Cp-treated homo, compared to Cp-treated WT mice. Of note, GPER1 deletion elicited a remarkable increase in renal apoptosis; however, no genotypic differences in cell proliferation were observed. Cp augmented kidney Ki67-positive counts, regardless of the genotype. Overall, our data do not support a role for GPER1 in mediating Cp-induced renal injury. GPER1 deletion promotes renal apoptosis and diminishes HO-1 induction in response to Cp, suggesting that GPER1 may play cytoprotective and anti-apoptotic actions in AKI. GPER1-induced regulation of HO-1 and apoptosis may offer novel therapeutic targets for the treatment of AKI.
Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage
Authors: Pawelec Paulina , Sypecka Joanna , Zalewska Teresa , Ziemka-Nalecz Malgorzata
Published: July 2022

The histone deacetylase inhibitor (HDACi) Givinostat/ITF2357 provides neuroprotection in adult models of brain injury; however, its action after neonatal hypoxia-ischemia (HI) is still undefined. The aim of our study was to test the hypothesis that the mechanism of Givinostat is associated with the alleviation of inflammation. For this purpose, we analyzed the microglial response and the effect on molecular mediators (chemokines/cytokines) that are crucial for inducing cerebral damage after neonatal hypoxia-ischemia. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 60 min of hypoxia (7.6% O2). Givinostat (10 mg/kg b/w) was administered in a 5-day regimen. The effects of Givinostat on HI-induced inflammation (cytokine, chemokine and microglial activation and polarization) were assessed with a Luminex assay, immunohistochemistry and Western blot. Givinostat treatment did not modulate the microglial response specific for HI injury. After Givinostat administration, the investigated chemokines and cytokines remained at the level induced by HI. The only immunosuppressive effect of Givinostat may be associated with the decrease in MIP-1α. Neonatal hypoxia-ischemia produces an inflammatory response by activating the proinflammatory M1 phenotype of microglia, disrupting the microglia–neuron (CX3CL1/CX3CR1) axis and elevating numerous proinflammatory cytokines/chemokines. Givinostat/ITF2357 did not prevent an inflammatory reaction after HI.
Therapy-Induced Senescent/Polyploid Cancer Cells Undergo Atypical Divisions Associated with Altered Expression of Meiosis, Spermatogenesis and EMT Genes
Authors: Czarnecka-Herok Joanna , Sliwinska Malgorzata Alicja , Herok Marcin , Targonska Alicja , Strzeszewska-Potyrala Anna , Bojko Agnieszka , Wolny Artur , Mosieniak Grazyna , Sikora Ewa
Published: July 2022

Upon anticancer treatment, cancer cells can undergo cellular senescence, i.e., the temporal arrest of cell division, accompanied by polyploidization and subsequent amitotic divisions, giving rise to mitotically dividing progeny. In this study, we sought to further characterize the cells undergoing senescence/polyploidization and their propensity for atypical divisions. We used p53-wild type MCF-7 cells treated with irinotecan (IRI), which we have previously shown undergo senescence/polyploidization. The propensity of cells to divide was measured by a BrdU incorporation assay, Ki67 protein level (cell cycle marker) and a time-lapse technique. Advanced electron microscopy-based cell visualization and bioinformatics for gene transcription analysis were also used. We found that after IRI-treatment of MCF-7 cells, the DNA replication and Ki67 level decreased temporally. Eventually, polyploid cells divided by budding. With the use of transmission electron microscopy, we showed the presence of mononuclear small cells inside senescent/polyploid ones. A comparison of the transcriptome of senescent cells at day three with day eight (when cells just start to escape senescence) revealed an altered expression of gene sets related to meiotic cell cycles, spermatogenesis and epithelial–mesenchymal transition. Although chemotherapy (DNA damage)-induced senescence is indispensable for temporary proliferation arrest of cancer cells, this response can be followed by their polyploidization and reprogramming, leading to more fit offspring.
Deep Molecular Characterization of Milder Spinal Muscular Atrophy Patients Carrying the c.859G>C Variant in SMN2
Authors: Blasco-Pérez Laura , Costa-Roger Mar , Leno-Colorado Jordi , Bernal Sara , Alias Laura , Codina-Solà Marta , Martínez-Cruz Desirée , Castiglioni Claudia , Bertini Enrico , Travaglini Lorena , Millán José M. , Aller Elena , Sotoca Javier , Juntas Raúl , Hoei-Hansen Christina Engel , Moreno-Escribano Antonio , Guillén-Navarro Encarna , Costa-Comellas Laura , Munell Francina , Boronat Susana , Rojas-García Ricardo , Povedano Mónica , Cuscó Ivon , Tizzano Eduardo F.
Published: July 2022

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype–phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype–phenotype correlations and improve prognostic outcomes.
An Association between Insulin Resistance and Neurodegeneration in Zebrafish Larval Model (Danio rerio)
Authors: Md Razip Nurliyana Najwa , Mohd Noor Suzita , Norazit Anwar , Nordin Norshariza , Sakeh Nurshafika Mohd , Khaza’ai Huzwah
Published: July 2022

Background: Type 2 diabetes mellitus has recently been identified as a mediator of neurodegeneration. However, the molecular mechanisms have not been clearly elucidated. We aimed to investigate insulin resistance associated with neurodegenerative events in zebrafish larvae. Methods: Larvae aged 72 h-post-fertilization (hpf) were induced to insulin resistance by immersion in 250 nM insulin and were then reinduced with 100 nM insulin at 96 hpf. This model was validated by a glucose levels assay, qPCR analysis of selected genes (akt, pepck, zglut3 and claudin-5a) and Oil Red-O (ORO) staining of the yolk sac for lipid distribution. The association of insulin resistance and neurodegeneration was validated by malondialdehyde (MDA), glutathione (GSH) assays, and by integrating next-generation sequencing with database for annotation, visualization and integrated discovery (DAVID). Results: There was a significant increase in glucose levels at 180 min in the insulin-resistant group. However, it decreased at 400 min after the re-challenge. Insulin-signaling mediators, akt and pepck, were showed significantly downregulated up to 400 min after insulin immersion (p < 0.05). Meanwhile, claudin-5a assessed blood–brain barrier (BBB) integrity and showed significant deterioration after 400 min of post-insulin immersion. ORO staining remarked the increase in yolk sac size in the insulin-resistant group. After the confirmation of insulin resistance, MDA levels increased significantly in the insulin-resistant group compared to the control group in the following parameters. Furthermore, dysregulated MAPK- and Wnt/Ca2+-signaling pathways were observed in the insulin-resistant group, disrupting energy metabolism and causing BBB injury. Conclusions: We conclude that the insulin-resistant zebrafish larvae alter the metabolic physiology associated with neurodegeneration.
Plant DNA Methylation: An Epigenetic Mark in Development, Environmental Interactions, and Evolution
Authors: Lucibelli Francesca , Valoroso Maria Carmen , Aceto Serena
Published: July 2022

DNA methylation is an epigenetic modification of the genome involved in the regulation of gene expression and modulation of chromatin structure. Plant genomes are widely methylated, and the methylation generally occurs on the cytosine bases through the activity of specific enzymes called DNA methyltransferases. On the other hand, methylated DNA can also undergo demethylation through the action of demethylases. The methylation landscape is finely tuned and assumes a pivotal role in plant development and evolution. This review illustrates different molecular aspects of DNA methylation and some plant physiological processes influenced by this epigenetic modification in model species, crops, and ornamental plants such as orchids. In addition, this review aims to describe the relationship between the changes in plant DNA methylation levels and the response to biotic and abiotic stress. Finally, we discuss the possible evolutionary implications and biotechnological applications of DNA methylation.
Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1
Authors: Machado Sarah E. , Spangler Daryll , Stacks Delores A. , Darley-Usmar Victor , Benavides Gloria A. , Xie Min , Balla József , Zarjou Abolfazl
Published: July 2022

Given the abundance of heme proteins (cytochromes) in the mitochondrion, it is evident that a meticulously orchestrated iron metabolism is essential for cardiac health. Here, we examined the functional significance of myocardial ferritin heavy chain (FtH) in a model of acute myocardial infarction. We report that FtH deletion did not alter either the mitochondrial regulatory and surveillance pathways (fission and fusion) or mitochondrial bioenergetics in response to injury. Furthermore, deletion of myocardial FtH did not affect cardiac function, assessed by measurement of left ventricular ejection fraction, on days 1, 7, and 21 post injury. To identify the modulated pathways providing cardiomyocyte protection coincident with FtH deletion, we performed unbiased transcriptomic analysis. We found that following injury, FtH deletion was associated with upregulation of several genes with anti-ferroptotic properties, including heme oxygenase-1 (HO-1) and the cystine/glutamate anti-porter (Slc7a11). These results suggested that HO-1 overexpression mitigates ferroptosis via upregulation of Slc7a11. Indeed, using transgenic mice with HO-1 overexpression, we demonstrate that overexpressed HO-1 is coupled with increased Slc7a11 expression. In conclusion, we demonstrate that following injury, myocardial FtH deletion leads to a compensatory upregulation in a number of anti-ferroptotic genes, including HO-1. Such HO-1 induction leads to overexpression of Slc7a11 and protects the heart against ischemia-reperfusion-mediated ferroptosis, preserves mitochondrial function, and overall function of the myocardium.
Paramylon and Other Bioactive Molecules in Micro and Macroalgae
Authors: Barsanti Laura , Birindelli Lorenzo , Gualtieri Paolo
Published: July 2022

Many algae synthesize compounds that have exceptional properties of nutraceutical, pharmacological, and biomedical interest. Pigments, fatty acids, phenols, and polysaccharides are among the main compounds investigated so far. Polysaccharides are the most exploited compounds, widely used in pharmaceutical, food, and chemical industries, which are at present entering into more advanced applications by gaining importance, from a therapeutic point of view, as antioxidant, antimicrobial, antitumor, and immunomodulatory agents. Establishing algae as an alternative supplement would complement the sustainable and environmental requirements in the framework of human health and well-being. This review focuses on the proprieties and uses of the main micro- and macroalgae metabolites, describing their potential for application in the different industrial sectors, from food/feed to chemical and pharmacological. Further, current technologies involved in bioactive molecule extraction strategies are documented.