bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity of Binge Eating Behavior among Overweight College Students in Taiwan and Associated Factors
Authors: Yan Huey-Yeu , Liu Chieh-Yu , Tseng Mei-Chih Meg , Lee Tzu-Ying , Mu Pei-Fan , Lin Hung-Ru
Published: January 2023

Background: Binge eating (BE) is considered a marker of obesity and overweight and a significant characteristic of feeding and eating disorders. Despite the high prevalence of obesity on college campuses, the issue of BE among college students in Taiwan has received little attention. The aim of this study was to investigate BE behavior among overweight college students in Taiwan and associated factors. Methods: This study utilized a cross-sectional survey. A total of 300 overweight college students were recruited through convenience sampling. Data were collected using a self-administered Binge Eating Scale (BES) and a body weight composition monitor (Model No. OMRON, HBF-126) and analyzed using descriptive statistics, correlation analysis, and regression analysis. Results: The average BES score was 10.67 (SD = 6.66, 0–34). With a BES score of 17 as the cut-off point, 17.3% (n = 52) of the participants were found to have moderate or severe BE behavior. Analysis of the demographic and psychosocial data using Spearman’s rho rank correlation coefficient revealed that sex, body mass index (BMI), uncontrolled eating, weight loss diets, academic stress, peer competition, interpersonal distress, and unpleasant or major life events were significantly correlated with BE behavior and its probability (rs = −0.14–0.15, p < 0.05). Furthermore, logistic regression analysis indicated that the odds ratio of the BES scores of female participants and those who stated to have experienced uncontrolled eating, weight loss diets, peer competition, and interpersonal distress was 1.05–6.04 times those of male participants and those without such experiences (p < 0.05). Conclusion: The study found that nearly one-fifth of participants presented moderate to severe levels of BE behaviors, and these were significantly correlated with sex and external environmental stress. This study suggests early intervention from campus psychological health personnel to provide proper therapy.
Prevalence and Factors Associated with Maternal Postpartum Depression among Mothers in Saudi Arabia: A Cross-Sectional Study
Authors: Abdelmola Amani Osman , Bahari Ahmed , Gosadi Ibrahim , Aburasain Khdeeja Shami , Osaisi Njoud Ali , Jilan Nidaa Sameer , Alsanosy Sarah Rashad , Mahnashi Haneen Ali , Gadri Hadeel Fuad , Khobrani Amnah Ahmad , Darraj Alaa Ahmad , Mahfouz Mohamed Salih , Kariri Hadi Dhafer Hassan , Abdelwahab Siddig Ibrahim
Published: January 2023

Postpartum depression (PPD) is a serious public health problem in many Middle Eastern countries. Mothers with PPD experience various extreme symptoms that affect their daily lives. This study aims to discover how common PPD is in the Jazan region, the most significant risk factors, and how likely depressed women are to seek help. An observational cross-sectional survey targeting a sample of 444 mothers in their first year after delivery using a pre-tested and validated EDPS standard tool to evaluate the prevalence of postpartum depression amongst them has been conducted. The data was collected and then analyzed using SPSS. Descriptive statistics and inferential statistics were used for data analysis. Multivariate logistic regression was used to assess the risk factors associated with PPD. The results indicate an extremely high prevalence of PPD in Jazan (75.7%). The prevalence of mothers having suicidal ideation was 6.3% quite often, 5.0% sometimes, and 7.9% hardly. Regarding the duration of depression symptoms, 34.78% were less than a month, 20.72% were less than six months, and 13.06% were less than one year. The study shows that the development of depression symptoms occurred within less than a week for 30.4% of the women. The most significant association with PPD was a lack of family support, which significantly increased the risk of PPD (OR = 5.9; p-value < 0.001). The mothers who had unexpected pregnancies had a risk of PPD (OR = 2.5; p-value < 0.001). Current research has revealed a high prevalence of postpartum depression among mothers in the Jazan region and that it is associated with different risk factors that increase the probability of PPD development. Pregnant women need to raise their awareness about PPD and learn how to avoid or deal with it.
Fuzzy Unsteady-State Drainage Solution for Land Reclamation
Authors: Tzimopoulos Christos , Samarinas Nikiforos , Papadopoulos Kyriakos , Evangelides Christos
Published: January 2023

Very well-drained lands could have a positive impact in various soil health indicators such as soil erosion and soil texture. A drainage system is responsible for properly aerated soil. Until today, in order to design a drainage system, a big challenge remained to find the subsurface drain spacing because many of the soil and hydraulic parameters present significant uncertainties. This fact also creates uncertainties to the overall physical problem solution, which, if not included in the preliminary design studies and calculations, could have bad consequences for the cultivated lands and soils. Finding the drain spacing requires the knowledge of the unsteady groundwater movement, which is described by the linear Boussinesq equation (Glover-Dumm equation). In this paper, the Adomian solution to the second order unsteady linear fuzzy partial differential one-dimensional Boussinesq equation is presented. The physical problem concerns unsteady drain spacing in a semi-infinite unconfined aquifer. The boundary conditions, with an initially horizontal water table, are considered fuzzy and the overall problem is translated to a system of crisp boundary value problems. Consequently, the crisp problem is solved using an Adomian decomposition method (ADM) and useful practical results are presented. In addition, by application of the possibility theory, the fuzzy results are translated into a crisp space, enabling the decision maker to make correct decisions about both the drain spacing and the future soil health management practices, with a reliable degree of confidence.
Internet Gaming Disorder Does Not Predict Mood, Anxiety or Substance Use Disorders in University Students: A One-Year Follow-Up Study
Authors: Borges Guilherme , Benjet Corina , Orozco Ricardo , Albor Yesica , Contreras Eunice V. , Monroy-Velasco Iris R. , Hernández-Uribe Praxedis C. , Báez-Mansur Patricia M. , Covarrubias Diaz Couder María A. , Quevedo-Chávez Guillermo E. , Gutierrez-García Raúl A. , Machado Nydia
Published: January 2023

We seek to evaluate whether Internet Gaming Disorder (IGD) among university students in Mexico during their first year at university predicts a long list of mental disorders a year later, controlling for baseline mental health disorders as well as demographics. This is a prospective cohort study with a one-year follow-up period conducted during the 2018–2019 academic year and followed up during the 2019–2020 academic year at six Mexican universities. Participants were first-year university students (n = 1741) who reported symptoms compatible with an IGD diagnosis at entry (baseline). Outcomes are seven mental disorders (mania, hypomania, and major depressive episodes; generalized anxiety disorder and panic disorder; alcohol use disorder and drug use disorder), and three groups of mental disorders (mood, anxiety, and substance use disorders) at the end of the one-year follow-up. Fully adjusted models, that included baseline controls for groups of mental disorders, rendered all associations null. The association between baseline IGD and all disorders and groups of disorders at follow-up was close to one, suggesting a lack of longitudinal impact of IGD on mental disorders. Conflicting results from available longitudinal studies on the role of IGD in the development of mental disorders warrant further research.
The Effect of Starting Blood Glucose Levels on Serum Electrolyte Concentrations during and after Exercise in Type 1 Diabetes
Authors: Momeni Zeinab , Boulé Normand G. , Prado Carla M. , Hinz Heather A. , Yardley Jane E.
Published: January 2023

Fear of hypoglycemia is a major exercise barrier for people with type 1 diabetes (PWT1D). Consequently, although guidelines recommend starting exercise with blood glucose (BG) concentration at 7–10 mmol/L, PWT1D often start higher, potentially affecting hydration and serum electrolyte concentrations. To test this, we examined serum and urine electrolyte concentrations during aerobic exercise (cycling 45 min at 60%VO2peak) in 12 PWT1D (10F/2M, mean ± SEM: age 29 ± 2.3 years, VO2peak 37.9 ± 2.2 mL·kg−1·min−1) with starting BG levels: 8–10 (MOD), and 12–14 (HI) mmol/L. Age, sex, and fitness-matched controls without diabetes (CON) completed one exercise session with BG in the normal physiological range. Serum glucose was significantly higher during exercise and recovery in HI versus MOD (p = 0.0002 and p < 0.0001, respectively) and in MOD versus CON (p < 0.0001). During exercise and recovery, MOD and HI were not significantly different in serum insulin (p = 0.59 and p = 0.63), sodium (p = 0.058 and p = 0.08), potassium (p = 0.17 and p = 0.16), calcium (p = 0.75 and 0.19), and magnesium p = 0.24 and p = 0.09). Our findings suggest that exercise of moderate intensity and duration with higher BG levels may not pose an immediate risk to hydration or serum electrolyte concentrations for PWT1D.
Usage of Children’s Makeup and Body Products in the United States and Implications for Childhood Environmental Exposures
Authors: Medley Eleanor A. , Kruchten Kendall E. , Spratlen Miranda J. , Ureño Maricela , Cole Anabel , Joglekar Rashmi , Herbstman Julie B.
Published: January 2023

There is growing evidence of toxicity associated with ingredients found in cosmetics and personal care products. Children’s makeup and body products (CMBPs) are widely marketed to children throughout the US; however, little is known about how and why children use them. We administered a survey to parents/guardians of children aged ≤12 years about the use of CMBPs. Among all the children (n = 312) of survey respondents (n = 207), 219 (70%) have used CMBPs in their lifetime. Older children used CMBPs at higher rates than younger children, and female children used CMBPs at higher rates than male children. Children of Hispanic/Latinx parents/guardians used CMBPs more often and for shorter durations and a greater proportion used lip, hair, and fragrance products than children of non-Hispanic parents/guardians. Approximately half the children that use CMBPs were reported to use them with play intentions. Compared to children of non-Hispanic parents/guardians, children of Hispanic/Latinx parents/guardians reported more play motivations for CMBP use. Using qualitative analysis approaches, responses suggest CMBPs are commonly used for fun or play activities. This mixed methods analysis serves as an introduction to understanding early life exposures to this unique and understudied class of products.
The Effect of Farmland Transfer on Agricultural Green Total Factor Productivity: Evidence from Rural China
Authors: Ma Guoqun , Dai Xiaopeng , Luo Yuxi
Published: January 2023

Exploring the effect and mechanism of farmland transfer on agricultural green total factor productivity (AGTFP) in China is of great significance for exerting the effectiveness of China’s farmland transfer policy and promoting green agricultural development. Based on panel data from 30 provinces from 2005 to 2020, this paper applies a two-way fixed effects model to analyze the impact of farmland transfer on AGTFP, and the mechanism of farmland transfer on AGTFP is also investigated. We find that farmland transfer has a significant and sound promoting effect on AGTFP, with respect to multiple robustness checks; there is heterogeneity regarding the impact of farmland transfer on AGTFP in terms of food functions, and farmland transfer can promote regional AGTFP through nonagricultural labor transfer and agricultural technology utilization. When considering the fact that farmland transfer has increased China’s AGTFP, the Chinese government should continue to adhere to the farmland transfer policy, accelerate nonagricultural labor transfer, improve the level of agricultural technology utilization, and ultimately promote green agricultural development.
Impact of the COVID-19 Pandemic on Psychosocial Well-being and Adaptation in Children and Adolescents with Asperger’s Syndrome
Authors: Tremolada Marta , Rosa Mariangela , Incardona Roberta Maria , Taverna Livia , Guidi Michele
Published: January 2023

Mental health could worsen in children and adolescents with autism spectrum disorder during the COVID-19 pandemic. In addition, their parents could be more at risk for an increase in anxiety and depression symptomatology. This study aims to understand the adaptation and the psychosocial well-being in a sample of 16 males aged 10–21 years old with Asperger’s syndrome after the quarantine for COVID-19 when they return to school and partially to their activities in September 2020. The adopted approach is multi-informant with a battery of questionnaires on psychological health and adaptation given by a secure online web data Qualtrics both to adolescents and also to their parents. Paralleling matched peers with typical developments were assessed by adopting the same methodology. The results evidenced several difficulties in psychological health in population with Asperger’s syndrome, especially in anxiety and socialization. Adaptation is put in crisis, even if they reported a good comprehension and adoption of the right behaviors anti-COVID-19. Parents of children with Asperger’s syndrome reported similar psychological difficulties and general health to those of the group of children typically developing. Some clinical indications could be discussed for psychologists who follow children and adolescents with Asperger’s syndrome.
Closing the Gap: From Research to Practice in Mental Health Interventions
Authors: Lipskaya-Velikovsky Lena , Krupa Terry
Published: January 2023

Evidence-based practice is critical but challenging in mental health. Rigorous research-proven interventions often do not yield expected results in the clinical practice. This study aimed to explore factors contributing to the effectiveness of Occupational Connections (OC)—an intervention for promotion of engagement in meaningful occupations in serious mental illness (SMI)—based on case series study of three quasi-experimental studies. The studies focused on people with SMI, admitted to intensive mental health services participated in the OC, as well as on a control condition group. Similar evaluation procedures throughout these studies addressed primary outcomes of participation dimensions and recovery orientation, as well as secondary outcomes of functional capacity, cognition, and symptom severity. Patterns of changes in outcome measures varied between the three studies as to direction and extension. In the OC groups, 29–60% of the outcome measurements were changed, in comparison to 29–43% of measurements in the control groups. The secondary outcomes were consistently improved in the OC (18–100% of measurements) in comparison to the control (18–67%). The analysis of the studies revealed that clinical effectiveness of participation-oriented intervention varied dependent on interplay between the clinical context, clinician actions, served persons’ characteristics, and evidence-building process. These factors should be considered to maximize research benefits for practice.
Comparative Transcriptome Analysis of the Heterosis of Salt Tolerance in Inter-Subspecific Hybrid Rice
Authors: Huang Zhibo , Ye Jing , Zhai Rongrong , Wu Mingming , Yu Faming , Zhu Guofu , Wang Zhoufei , Zhang Xiaoming , Ye Shenghai
Published: January 2023

Soil salinity is one of the major abiotic stresses limiting rice growth. Hybrids outperform their parents in salt tolerance in rice, while its mechanism is not completely understood. In this study, a higher seedling survival was observed after salt treatment in an inter-subspecific hybrid rice, Zhegengyou1578 (ZGY1578), compared with its maternal japonica Zhegeng7A (ZG7A) and paternal indica Zhehui1578 (ZH1578). A total of 2584 and 3061 differentially expressed genes (DEGs) with at least twofold changes were identified between ZGY1578 and ZG7A and between ZGY1578 and ZH1578, respectively, in roots under salt stress using the RNA sequencing (RNA-Seq) approach. The expressions of a larger number of DEGs in hybrid were lower or higher than those of both parents. The DEGs associated with transcription factors, hormones, and reactive oxygen species (ROS)–related genes might be involved in the heterosis of salt tolerance. The expressions of the majority of transcription factors and ethylene-, auxin-, and gibberellin-related genes, as well as peroxidase genes, were significantly higher in the hybrid ZGY1578 compared with those of both parents. The identified genes provide valuable clues to elucidate the heterosis of salt tolerance in inter-subspecific hybrid rice.
Neurogenic Hypertension, the Blood–Brain Barrier, and the Potential Role of Targeted Nanotherapeutics
Authors: Lamptey Richard Nii Lante , Sun Chengwen , Layek Buddhadev , Singh Jagdish
Published: January 2023

Hypertension is a major health concern globally. Elevated blood pressure, initiated and maintained by the brain, is defined as neurogenic hypertension (NH), which accounts for nearly half of all hypertension cases. A significant increase in angiotensin II-mediated sympathetic nervous system activity within the brain is known to be the key driving force behind NH. Blood pressure control in NH has been demonstrated through intracerebrovascular injection of agents that reduce the sympathetic influence on cardiac functions. However, traditional antihypertensive agents lack effective brain permeation, making NH management extremely challenging. Therefore, developing strategies that allow brain-targeted delivery of antihypertensives at the therapeutic level is crucial. Targeting nanotherapeutics have become popular in delivering therapeutics to hard-to-reach regions of the body, including the brain. Despite the frequent use of nanotherapeutics in other pathological conditions such as cancer, their use in hypertension has received very little attention. This review discusses the underlying pathophysiology and current management strategies for NH, as well as the potential role of targeted therapeutics in improving current treatment strategies.
To Kill or to Be Killed: How Does the Battle between the UPS and Autophagy Maintain the Intracellular Homeostasis in Eukaryotes?
Authors: Yu Peifeng , Hua Zhihua
Published: January 2023

The ubiquitin-26S proteasome system and autophagy are two major protein degradation machineries encoded in all eukaryotic organisms. While the UPS is responsible for the turnover of short-lived and/or soluble misfolded proteins under normal growth conditions, the autophagy-lysosomal/vacuolar protein degradation machinery is activated under stress conditions to remove long-lived proteins in the forms of aggregates, either soluble or insoluble, in the cytoplasm and damaged organelles. Recent discoveries suggested an integrative function of these two seemly independent systems for maintaining the proteome homeostasis. One such integration is represented by their reciprocal degradation, in which the small 76-amino acid peptide, ubiquitin, plays an important role as the central signaling hub. In this review, we summarized the current knowledge about the activity control of proteasome and autophagosome at their structural organization, biophysical states, and turnover levels from yeast and mammals to plants. Through comprehensive literature studies, we presented puzzling questions that are awaiting to be solved and proposed exciting new research directions that may shed light on the molecular mechanisms underlying the biological function of protein degradation.
Complexes of Cationic Pyridylphenylene Dendrimers with Anionic Liposomes: The Role of Dendrimer Composition in Membrane Structural Changes
Authors: Efimova Anna A. , Sorokina Svetlana A. , Trosheva Kseniya S. , Yaroslavov Alexander A. , Shifrina Zinaida B.
Published: January 2023

In the last decades, dendrimers have received attention in biomedicine that requires detailed study on the mechanism of their interaction with cell membranes. In this article, we report on the role of dendrimer structure in their interaction with liposomes. Here, the interactions between cationic pyridylphenylene dendrimers of the first, second, and third generations with mixed or completely charged pyridyl periphery (D16+, D215+, D229+, and D350+) with cholesterol-containing (CL/Chol/DOPC) anionic liposomes were investigated by microelectrophoresis, dynamic light scattering, fluorescence spectroscopy, and conductometry. It was found that the architecture of the dendrimer, namely the generation, the amount of charged pyridynium groups, the hydrophobic phenylene units, and the rigidity of the spatial structure, determined the special features of the dendrimer–liposome interactions. The binding of D350+ and D229+ with almost fully charged peripheries to liposomes was due to electrostatic forces: the dendrimer molecules could be removed from the liposomal surfaces by NaCl addition. D350+ and D229+ did not display a disruptive effect toward membranes, did not penetrate into the hydrophobic lipid bilayer, and were able to migrate between liposomes. For D215+, a dendrimer with a mixed periphery, hydrophobic interactions of phenylene units with the hydrocarbon tails of lipids were observed, along with electrostatic complexation with liposomes. As a result, defects were formed in the bilayer, which led to irreversible interactions with lipid membranes wherein there was no migration of D215+ between liposomes. A first-generation dendrimer, D16+, which was characterized by small size, a high degree of hydrophobicity, and a rigid structure, when interacting with liposomes caused significant destruction of liposomal membranes. Evidently, this interaction was irreversible: the addition of salt did not lead to the dissociation of the complex.
Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy
Authors: Dubinin Mikhail V. , Belosludtsev Konstantin N.
Published: January 2023

Duchenne muscular dystrophy (DMD) is caused by the absence of the dystrophin protein and a properly functioning dystrophin-associated protein complex (DAPC) in muscle cells. DAPC components act as molecular scaffolds coordinating the assembly of various signaling molecules including ion channels. DMD shows a significant change in the functioning of the ion channels of the sarcolemma and intracellular organelles and, above all, the sarcoplasmic reticulum and mitochondria regulating ion homeostasis, which is necessary for the correct excitation and relaxation of muscles. This review is devoted to the analysis of current data on changes in the structure, functioning, and regulation of the activity of ion channels in striated muscles in DMD and their contribution to the disruption of muscle function and the development of pathology. We note the prospects of therapy based on targeting the channels of the sarcolemma and organelles for the correction and alleviation of pathology, and the problems that arise in the interpretation of data obtained on model dystrophin-deficient objects.
The Utility of Amino Acid Metabolites in the Diagnosis of Major Depressive Disorder and Correlations with Depression Severity
Authors: Ho Cyrus Su Hui , Tay Gabrielle Wann Nii , Wee Hai Ning , Ching Jianhong
Published: January 2023

Major depressive disorder (MDD) is a highly prevalent and disabling condition with a high disease burden. There are currently no validated biomarkers for the diagnosis and treatment of MDD. This study assessed serum amino acid metabolite changes between MDD patients and healthy controls (HCs) and their association with disease severity and diagnostic utility. In total, 70 MDD patients and 70 HCs matched in age, gender, and ethnicity were recruited for the study. For amino acid profiling, serum samples were analysed and quantified by liquid chromatography-mass spectrometry (LC-MS). Receiver-operating characteristic (ROC) curves were used to classify putative candidate biomarkers. MDD patients had significantly higher serum levels of glutamic acid, aspartic acid and glycine but lower levels of 3-Hydroxykynurenine; glutamic acid and phenylalanine levels also correlated with depression severity. Combining these four metabolites allowed for accurate discrimination of MDD patients and HCs, with 65.7% of depressed patients and 62.9% of HCs correctly classified. Glutamic acid, aspartic acid, glycine and 3-Hydroxykynurenine may serve as potential diagnostic biomarkers, whereas glutamic acid and phenylalanine may be markers for depression severity. To elucidate the association between these indicators and clinical features, it is necessary to conduct additional studies with larger sample sizes that involve a spectrum of depressive symptomatology.
Interaction of High-Molecular Weight Fucoidan from Laminaria hyperborea with Natural Functions of the Retinal Pigment Epithelium
Authors: Dörschmann Philipp , Kopplin Georg , Roider Johann , Klettner Alexa
Published: January 2023

Fucoidans are polysaccharides and constituents of cell walls of brown algae such as Laminaria hyperborea (LH). They exhibit promising effects regarding age-related macular degeneration (AMD). However, the safety of this compound needs to be assured. The focus of this study lies on influences of an LH fucoidan on the retinal pigment epithelium (RPE). The high-molecular weight LH fucoidan Fuc1 was applied to primary porcine RPE cells, and a tetrazolium (MTT) cell viability assay was conducted. Further tests included a scratch assay to measure wound healing, Western blotting to measure expression of retinal pigment epithelium-specific 65 kDa protein (RPE65), as well as immunofluorescence to measure uptake of opsonized fluorescence beads into RPE cells. Lipopolysaccharide was used to proinflammatorily activate the RPE, and interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion was measured. RPE/choroid cultures were used to assess vascular endothelial growth factor (VEGF) secretion. Real-time polymerase chain reaction (real-time PCR) was performed to detect the gene expression of 91 different genes in a specific porcine RPE gene array. Fuc1 slightly reduced wound healing, but did not influence cell viability, phagocytosis or RPE65 expression. Fuc1 lowered IL-6, IL-8 and VEGF secretion. Furthermore, Fuc1 did not change tested RPE genes. In conclusion, Fuc1 does not impair RPE cellular functions and shows antiangiogenic and anti-inflammatory activities, which indicates its safety and strengthens its suitability concerning ocular diseases.
Gut Microbiome Proteomics in Food Allergies
Authors: Abril Ana G. , Carrera Mónica , Sánchez-Pérez Ángeles , Villa Tomás G.
Published: January 2023

Food allergies (FA) have dramatically increased in recent years, particularly in developed countries. It is currently well-established that food tolerance requires the strict maintenance of a specific microbial consortium in the gastrointestinal (GI) tract microbiome as alterations in the gut microbiota can lead to dysbiosis, causing inflammation and pathogenic intestinal conditions that result in the development of FA. Although there is currently not enough knowledge to fully understand how the interactions between gut microbiota, host responses and the environment cause food allergies, recent advances in ‘-omics’ technologies (i.e., proteomics, genomics, metabolomics) and in approaches involving systems biology suggest future headways that would finally allow the scientific understanding of the relationship between gut microbiome and FA. This review summarizes the current knowledge in the field of FA and insights into the future advances that will be achieved by applying proteomic techniques to study the GI tract microbiome in the field of FA and their medical treatment. Metaproteomics, a proteomics experimental approach of great interest in the study of GI tract microbiota, aims to analyze and identify all the proteins in complex environmental microbial communities; with shotgun proteomics, which uses liquid chromatography (LC) for separation and tandem mass spectrometry (MS/MS) for analysis, as it is the most promising technique in this field.
Crystal Structure of Inhibitor-Bound Bacterial Oligopeptidase B in the Closed State: Similarity and Difference between Protozoan and Bacterial Enzymes
Authors: Petrenko Dmitry E. , Karlinsky David M. , Gordeeva Veronika D. , Arapidi Georgij P. , Britikova Elena V. , Britikov Vladimir V. , Nikolaeva Alena Y. , Boyko Konstantin M. , Timofeev Vladimir I. , Kuranova Inna P. , Mikhailova Anna G. , Bocharov Eduard V. , Rakitina Tatiana V.
Published: January 2023

The crystal structure of bacterial oligopeptidase B from Serratia proteamaculans (SpOpB) in complex with a chloromethyl ketone inhibitor was determined at 2.2 Å resolution. SpOpB was crystallized in a closed (catalytically active) conformation. A single inhibitor molecule bound simultaneously to the catalytic residues S532 and H652 mimicked a tetrahedral intermediate of the catalytic reaction. A comparative analysis of the obtained structure and the structure of OpB from Trypanosoma brucei (TbOpB) in a closed conformation showed that in both enzymes, the stabilization of the D-loop (carrying the catalytic D) in a position favorable for the formation of a tetrahedral complex occurs due to interaction with the neighboring loop from the β-propeller. However, the modes of interdomain interactions were significantly different for bacterial and protozoan OpBs. Instead of a salt bridge (as in TbOpB), in SpOpB, a pair of polar residues following the catalytic D617 and a pair of neighboring arginine residues from the β-propeller domain formed complementary oppositely charged surfaces. Bioinformatics analysis and structural modeling show that all bacterial OpBs can be divided into two large groups according to these two modes of D-loop stabilization in closed conformations.
Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens
Authors: Schossig Paul , Coskun Ebru , Arsenic Ruza , Horst David , Sehouli Jalid , Bergmann Eva , Andresen Nadine , Sigler Christian , Busse Antonia , Keller Ulrich , Ochsenreither Sebastian
Published: January 2023

Adoptive T cell-receptor therapy (ACT) could represent a promising approach in the targeted treatment of epithelial ovarian cancer (EOC). However, the identification of suitable tumor-associated antigens (TAAs) as targets is challenging. We identified and prioritized TAAs for ACT and other immunotherapeutic interventions in EOC. A comprehensive list of pre-described TAAs was created and candidates were prioritized, using predefined weighted criteria. Highly ranked TAAs were immunohistochemically stained in a tissue microarray of 58 EOC samples to identify associations of TAA expression with grade, stage, response to platinum, and prognosis. Preselection based on expression data resulted in 38 TAAs, which were prioritized. Along with already published Cyclin A1, the TAAs KIF20A, CT45, and LY6K emerged as most promising targets, with high expression in EOC samples and several identified peptides in ligandome analysis. Expression of these TAAs showed prognostic relevance independent of molecular subtypes. By using a systematic vetting algorithm, we identified KIF20A, CT45, and LY6K to be promising candidates for immunotherapy in EOC. Results are supported by IHC and HLA-ligandome data. The described method might be helpful for the prioritization of TAAs in other tumor entities.
A Novel Role of the Two-Component System Response Regulator UvrY in Enterohemorrhagic Escherichia coli O157:H7 Pathogenicity Regulation
Authors: Wu Pan , Wang Qian , Yang Qian , Feng Xiaohui , Liu Xingmei , Sun Hongmin , Yan Jun , Kang Chenbo , Liu Bin , Liu Yutao , Yang Bin
Published: January 2023

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important human pathogen causing severe diseases, such as hemorrhagic colitis and lethal hemolytic uremic syndrome. The signal-sensing capability of EHEC O157:H7 at specific host colonization sites via different two-component systems (TCSs) is closely related to its pathogenicity during infection. However, the types of systems involved and the regulatory mechanisms are not fully understood. Here, we investigated the function of the TCS BarA/UvrY regulator UvrY in the pathogenicity regulation of EHEC O157:H7. Our results showed that UvrY acts as a positive regulator of EHEC O157:H7 for cellular adherence and mouse colonization through the transcriptional activation of the locus for enterocyte effacement (LEE) pathogenic genes. Furthermore, this regulation is mediated by the LEE island master regulator, Ler. Our results highlight the significance of UvrY in EHEC O157:H7 pathogenicity and underline the unknown importance of BarA/UvrY in colonization establishment and intestinal adaptability during infection.
Challenges of Gene Editing Therapies for Genodermatoses
Authors: Brooks Imogen R. , Sheriff Adam , Moran Declan , Wang Jingbo , Jacków Joanna
Published: January 2023

Genodermatoses encompass a wide range of inherited skin diseases, many of which are monogenic. Genodermatoses range in severity and result in early-onset cancers or life-threatening damage to the skin, and there are few curative options. As such, there is a clinical need for single-intervention treatments with curative potential. Here, we discuss the nascent field of gene editing for the treatment of genodermatoses, exploring CRISPR–Cas9 and homology-directed repair, base editing, and prime editing tools for correcting pathogenic mutations. We specifically focus on the optimisation of editing efficiency, the minimisation off-targets edits, and the tools for delivery for potential future therapies. Honing each of these factors is essential for translating gene editing therapies into the clinical setting. Therefore, the aim of this review article is to raise important considerations for investigators aiming to develop gene editing approaches for genodermatoses.
Regulation of Cortico-Thalamic JNK1/2 and ERK1/2 MAPKs and Apoptosis-Related Signaling Pathways in PDYN Gene-Deficient Mice Following Acute and Chronic Mild Stress
Authors: Yáñez-Gómez Fernando , Ramos-Miguel Alfredo , García-Sevilla Jesús A. , Manzanares Jorge , Femenía Teresa
Published: January 2023

The crosstalk between the opioidergic system and mitogen-activated protein kinases (MAPKs) has a critical role in mediating stress-induced behaviors related to the pathophysiology of anxiety. The present study evaluated the basal status and stress-induced alterations of cortico-thalamic MAPKs and other cell fate-related signaling pathways potentially underlying the anxiogenic endophenotype of PDYN gene-deficient mice. Compared to littermates, PDYN knockout (KO) mice had lower cortical and or thalamic amounts of the phospho-activated MAPKs c-Jun N-terminal kinase (JNK1/2) and extracellular signal-regulated kinase (ERK1/2). Similarly, PDYN-KO animals displayed reduced cortico-thalamic densities of total and phosphorylated (at Ser191) species of the cell fate regulator Fas-associated protein with death domain (FADD) without alterations in the Fas receptor. Exposure to acute restraint and chronic mild stress stimuli induced the robust stimulation of JNK1/2 and ERK1/2 MAPKs, FADD, and Akt-mTOR pathways, without apparent increases in apoptotic rates. Interestingly, PDYN deficiency prevented stress-induced JNK1/2 and FADD but not ERK1/2 or Akt-mTOR hyperactivations. These findings suggest that cortico-thalamic MAPK- and FADD-dependent neuroplasticity might be altered in PDYN-KO mice. In addition, the results also indicate that the PDYN gene (and hence dynorphin release) may be required to stimulate JNK1/2 and FADD (but not ERK1/2 or Akt/mTOR) pathways under environmental stress conditions.
The BCO2 Genotype and the Expression of BCO1, BCO2, LRAT, and TTPA Genes in the Adipose Tissue and Brain of Rabbits Fed a Diet with Marigold Flower Extract
Authors: Strychalski Janusz , Gugołek Andrzej , Kaczorek-Łukowska Edyta , Antoszkiewicz Zofia , Matusevičius Paulius
Published: January 2023

This study was undertaken to evaluate the effect of the BCO2 genotype and dietary supplementation with marigold flower extract on the expression of BCO1, BCO2, LRAT, and TTPA genes in the adipose tissue and brain of rabbits. The concentrations of lutein, zeaxanthin, β-carotene, retinol, and α-tocopherol were determined in samples collected from rabbits. Sixty young male Termond White rabbits were allocated to three groups based on their genotype at codon 248 of the BCO2 gene (ins/ins, ins/del, and del/del). Each group comprised two subgroups; one subgroup was administered a standard diet, whereas the diet offered to the other subgroup was supplemented with 6 g/kg of marigold flower extract. The study demonstrated that the BCO2 genotype may influence the expression levels of the BCO2, LRAT, and TTPA genes in adipose tissue, and TTPA and BCO1 genes in the brain. Moreover, an increase in the amount of lutein in the diet of BCO2 del/del rabbits may increase the expression of BCO1, LRAT, and TTPA genes in adipose tissue, and the expression of the BCO2 gene in the brain. Another finding of the study is that the content of carotenoids and α-tocopherol increases in both the adipose tissue and brain of BCO2 del/del rabbits.
Defining the Role of the Gut Microbiome in the Pathogenesis and Treatment of Lymphoid Malignancies
Authors: Upadhyay Banskota Shristi , Skupa Sydney A. , El-Gamal Dalia , D’Angelo Christopher R.
Published: January 2023

The gut microbiome is increasingly being recognized as an important immunologic environment, with direct links to the host immune system. The scale of the gut microbiome’s genomic repertoire extends the capacity of its host’s genome by providing additional metabolic output, and the close communication between gut microbiota and mucosal immune cells provides a continued opportunity for immune education. The relationship between the gut microbiome and the host immune system has important implications for oncologic disease, including lymphoma, a malignancy derived from within the immune system itself. In this review, we explore past and recent discoveries describing the role that bacterial populations play in lymphomagenesis, diagnosis, and therapy. We highlight key relationships within the gut microbiome-immune-oncology axis that present exciting opportunities for directed interventions intended to shape the microbiome for therapeutic effect. We conclude with a limited summary of active clinical trials targeting the microbiome in hematologic malignancies, along with future directions on gut microbiome investigations within lymphoid malignancies.
Overview of Cellular and Soluble Mediators in Systemic Inflammation Associated with Non-Alcoholic Fatty Liver Disease
Authors: Marques Patrice , Francisco Vera , Martínez-Arenas Laura , Carvalho-Gomes Ângela , Domingo Elena , Piqueras Laura , Berenguer Marina , Sanz Maria-Jesus
Published: January 2023

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient’s death and/or the need for liver transplantation. Along with the high associated economic burden, the high mortality rate among NAFLD patients raises interest, not only in the search for novel therapeutic approaches, but also in early diagnosis and prevention to reduce the incidence of NAFLD-related complications. In this line, an exhaustive characterization of the immune status of patients with NAFLD is mandatory. Herein, we attempted to gather and compare the current and relevant scientific evidence on this matter, mainly on human reports. We addressed the current knowledge related to circulating cellular and soluble mediators, particularly platelets, different leukocyte subsets and relevant inflammatory soluble mediators.
The ATR Inhibitor VE-821 Enhances the Radiosensitivity and Suppresses DNA Repair Mechanisms of Human Chondrosarcoma Cells
Authors: Lohberger Birgit , Glänzer Dietmar , Eck Nicole , Stasny Katharina , Falkner Anna , Leithner Andreas , Georg Dietmar
Published: January 2023

To overcome the resistance to radiotherapy in chondrosarcomas, the prevention of efficient DNA repair with an additional treatment was explored for particle beams as well as reference X-ray irradiation. The combined treatment with DNA repair inhibitors—with a focus on ATRi VE-821—and proton or carbon ions irradiation was investigated regarding cell viability, proliferation, cell cycle distribution, MAPK phosphorylation, and the expression of key DNA repair genes in two human chondrosarcoma cell lines. Pre-treatment with the PARPis Olaparib or Veliparib, the ATMi Ku-55933, and the ATRi VE-821 resulted in a dose-dependent reduction in viability, whereas VE-821 has the most efficient response. Quantification of γH2AX phosphorylation and protein expression of the DNA repair pathways showed a reduced regenerative capacity after irradiation. Furthermore, combined treatment with VE-821 and particle irradiation increased MAPK phosphorylation and the expression of apoptosis markers. At the gene expression and at the protein expression/phosphorylation level, we were able to demonstrate the preservation of DNA damage after combined treatment. The present data showed that the combined treatment with ATMi VE-821 increases the radiosensitivity of human chondrosarcoma cells in vitro and significantly suppresses efficient DNA repair mechanisms, thus improving the efficiency of radiotherapy.
Characteristics of Solidified Carbon Dioxide and Perspectives for Its Sustainable Application in Sewage Sludge Management
Authors: Kazimierowicz Joanna , Dębowski Marcin
Published: January 2023

Appropriate management is necessary to mitigate the environmental impacts of wastewater sludge. One lesser-known technology concerns the use of solidified CO2 for dewatering, sanitization, and digestion improvement. Solidified CO2 is a normal byproduct of natural gas treatment processes and can also be produced by dedicated biogas upgrading technologies. The way solidified CO2 is sourced is fully in line with the principles of the circular economy and carbon dioxide mitigation. The aim of this review is to summarize the current state of knowledge on the production and application of solid CO2 in the pretreatment and management of sewage sludge. Using solidified CO2 for sludge conditioning causes effective lysis of microbial cells, which destroys activated sludge flocs, promotes biomass fragmentation, facilitates efficient dispersion of molecular associations, modifies cell morphology, and denatures macromolecules. Solidified CO2 can be used as an attractive tool to sanitize and dewater sludge and as a pretreatment technology to improve methane digestion and fermentative hydrogen production. Furthermore, it can also be incorporated into a closed CO2 cycle of biogas production–biogas upgrading–solidified CO2 production–sludge disintegration–digestion–biogas production. This feature not only bolsters the technology’s capacity to improve the performance and cost-effectiveness of digestion processes, but can also help reduce atmospheric CO2 emissions, a crucial advantage in terms of environment protection. This new approach to solidified CO2 generation and application largely counteracts previous limitations, which are mainly related to the low cost-effectiveness of the production process.
Specific microRNA Signature Kinetics in Porphyromonas gingivalis-Induced Periodontitis
Authors: Aravindraja Chairmandurai , Vekariya Krishna Mukesh , Botello-Escalante Ruben , Rahaman Shaik O. , Chan Edward K. L. , Kesavalu Lakshmyya
Published: January 2023

Porphyromonas gingivalis is one of the major bacteria constituting the subgingival pathogenic polymicrobial milieu during periodontitis. Our objective is to determine the global microRNA (miRNA, miR) expression kinetics in 8- and 16-weeks duration of P. gingivalis infection in C57BL/6J mice and to identify the miRNA signatures at specific time-points in mice. We evaluated differential expression (DE) miRNAs in mandibles (n = 10) using high-throughput NanoString nCounter® miRNA expression panels. The bacterial colonization, alveolar bone resorption (ABR), serum immunoglobulin G (IgG) antibodies, and bacterial dissemination were confirmed. In addition, all the infected mice showed bacterial colonization on the gingival surface, significant increases in ABR (p < 0.0001), and specific IgG antibody responses (p < 0.05–0.001). The miRNA profiling showed 26 upregulated miRNAs (e.g., miR-804, miR-690) and 14 downregulated miRNAs (e.g., miR-1902, miR-1937a) during an 8-weeks infection, whereas 7 upregulated miRNAs (e.g., miR-145, miR-195) and one downregulated miR-302b were identified during a 16-weeks infection. Both miR-103 and miR-30d were commonly upregulated at both time-points, and all the DE miRNAs were unique to the specific time-points. However, miR-31, miR-125b, miR-15a, and miR-195 observed in P. gingivalis-infected mouse mandibles were also identified in the gingival tissues of periodontitis patients. None of the previously identified miRNAs reported in in vitro studies using cell lines (periodontal ligament cells, gingival epithelial cells, human leukemia monocytic cell line (THP-1), and B cells) exposed to P. gingivalis lipopolysaccharide were observed in the in vivo study. Most of the pathways (endocytosis, bacterial invasion, and FcR-mediated phagocytosis) targeted by the DE miRNAs were linked with bacterial pathogen recognition and clearance. Further, eighteen miRNAs were closely associated with the bacterial invasion of epithelial cells. This study highlights the altered expression of miRNA in gingiva, and their expression depends on the time-points of infection. This is the first in vivo study that identified specific signature miRNAs (miR-103 and miR-30d) in P. gingivalis invasion of epithelial cells, establishes a link between miRNA and development of periodontitis and helping to better understand the pathobiology of periodontitis.