bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Quality of Guinea Fowl (Numida meleagris) Eggs from Free-Range Farming Depending on the Storage Period and Age of Laying Hens
Authors: Bucław Mateusz , Adaszyńska-Skwirzyńska Michalina , Majewska Danuta , Szczerbińska Danuta , Dzięcioł Małgorzata
Published: July 2024

The aim of the study was to determine the changes occurring in the eggs of helmeted guinea fowl (Numida meleagris) from free-range farming in relation to the laying season and storage time. The experimental material consisted of 360 guinea fowl eggs, collected in the first, second and third laying seasons and stored for 7, 14 and 21 days. After each period, physical and physicochemical characteristics of the eggs were determined, as well as the basic chemical composition and mineral content of the albumen and yolk and the yolk fatty acid profile. The age of the guinea fowls affected certain physical parameters of the eggs. The egg weight, shape index and shell thickness increased with the age of the laying hens; however, a decrease in the proportion of shell in the egg was demonstrated. Storage time had a significant effect on egg weight, weight loss during storage and air cell height. Significant differences were found in the chemical composition of guinea fowl eggs depending on the age of the laying hens. Eggs obtained from older laying hens were characterized by higher yolk fat content and lower ash content, while the albumen contained higher water content and lower ash content. During the three-year laying period, changes were observed in the mineral composition of the eggs. The fatty acid profile underwent significant changes; however, no important differences were observed in the total content of SFA, MUFA, PUFA and n-6 fatty acids. Conversely, significant differences were found for n-3 acids and the n-6/n-3 ratio. Eggs in the first and second laying seasons exhibited the most favorable composition. The slow dynamics of changes occurring in successive laying seasons and egg storage time indicated that the raw material studied was safe and could be used by consumers
Complete Chloroplast Genome of Megacarpaea megalocarpa and Comparative Analysis with Related Species from Brassicaceae
Authors: Zhang Zhuo , Shi Xiaojun , Tian Haowen , Qiu Juan , Ma Hanze , Tan Dunyan
Published: July 2024

Megacarpaea megalocarpa, a perennial herbaceous species belonging to the Brassicaceae family, has potential medicinal value. We isolated and characterized the chloroplast (cp) genome of M. megalocarpa and compared it with closely related species. The chloroplast genome displayed a typical quadripartite structure, spanning 154,877 bp, with an overall guanine–cytosine (GC) content of 36.20%. Additionally, this genome contained 129 genes, 105 simple sequence repeats (SSRs), and 48 long repeat sequences. Significantly, the ycf1 gene exhibited a high degree of polymorphism at the small single copy (SSC) region and the inverted repeat a (IRa) boundary. Despite this polymorphism, relative synonymous codon usage (RSCU) values were found to be similar across species, and no large segment rearrangements or inversions were detected. The large single copy (LSC) and SSC regions showed higher sequence variations and nucleotide polymorphisms compared to the IR region. Thirteen distinct hotspot regions were identified as potential molecular markers. Our selection pressure analysis revealed that the protein-coding gene rpl20 is subjected to different selection pressures in various species. Phylogenetic analysis positioned M. megalocarpa within the expanded lineage II of the Brassicaceae family. The estimated divergence time suggests that M. megalocarpa diverged approximately 4.97 million years ago. In summary, this study provides crucial baseline information for the molecular identification, phylogenetic relationships, conservation efforts, and utilization of wild resources in Megacarpaea.
Psychometric Properties of Jebsen Taylor Hand Function Test in an Italian Population with Parkinson’s Disease
Authors: Galeoto Giovanni , Berardi Anna , Simeon Rachele , Panuccio Francescaroberta , Fabbrini Giovanni , Belvisi Daniele , González-Bernal Jerónimo , Seco-Calvo Jesús Ángel
Published: July 2024

Background: Assessment of upper limb function is critical in the rehabilitation process of people with Parkinson’s Disease (PD), and universally validated outcome measures are needed to allow comparisons across the practice. Moreover, the study of psychometric properties of the same tool on different clinical populations guarantees the possibility of reliably evaluating the same rehabilitation treatment in people with different clinical conditions. Aim of the study: The aim of this research was to evaluate the psychometric characteristics of the Italian adaptation of the Jebsen Taylor Hand Function Test (JTHFT) in individuals with PD. Methods: The reliability and validity of the test were assessed in accordance with international standards. Internal consistency was measured using Cronbach’s alpha, and test–retest reliability was determined via the intraclass correlation coefficient (ICC). The construct validity and cross-cultural validity of the test were evaluated using Pearson’s correlation coefficient with three assessment tools on upper limb function, independence, and quality of life, with hand grip power measured by a dynamometer and an Italian pangram. Finally, responsiveness after a one month of rehabilitation treatment was measured using the Wilcoxon rank test. Results: Fifty-two Italian people with PD were recruited. Cronbach’s alpha values ranged from 0.556 (non-dominant hand) to 0.668 (dominant hand); ICC values ranged from 0.754 to 0.988. Construct validity showed that several statistically significant correlations were detected. Wilcoxon’s test showed that the assessment tool can detect a change in this population after treatment. Conclusions: The JTHFT is a reliable, valid, and respondent tool to evaluate the upper limb and hand functionalities in PD patients. It should be added to the toolkit for measuring upper limb performance in this population, adding value to clinical evaluation and ensuring comparable results for different clinical populations and different countries.
Exploratory Study on the Impact on Emotional Health Derived from Participation in an Inclusive Choir
Authors: Juan-Morera Borja , Nadal-García Icíar , López-Casanova Belén , Estella-Escobar Lucía
Published: July 2024

Participation in group activities such as choirs has been shown to have positive effects on emotional health and overall well-being. Inclusive choirs, which integrate individuals of various abilities and diverse backgrounds, provide a unique space for social interaction, emotional expression, and inclusion. This study aims to explore the impact of participation in an inclusive choir on the emotional health of its members, identifying both positive and negative emotional impacts as well as personal experiences derived from their participation. This longitudinal exploratory study combines participant observation, field notes, focus groups, and questionnaires to gain a deep understanding of the participant’s emotional experiences through their narratives. The study was conducted in an inclusive choir located in a medium-sized city in Spain, which brings together people of various ages, genders, abilities, and cultural backgrounds. The results indicated that most participants experienced significant improvements in their emotional well-being, including increased self-esteem, a greater sense of belonging, and reduced symptoms of anxiety and depression. Participants also reported that the choir provided a safe space for emotional expression and the building of meaningful relationships. Participation in an inclusive choir can have a considerable positive impact on the emotional health of its members.
An Evaluation of Patient Privacy Protection with Fuzzy Conjoint Analysis—A Case Study from Nurses’ Perspective
Authors: Gürsel Güney , Bayer Nükhet , Turunç Ömer , Çalışkan Abdullah , Akkoç İrfan , Demirci Ayhan , Çetin Melike , Köroğlu Özlem
Published: July 2024

Background: With the rapid improvement in healthcare technologies, the security and privacy of the most sensitive data are at risk. Patient privacy has many components, even when data are in electronic format. Although patient privacy has extensively been discussed in the literature, there is no study that has presented all components of patient privacy. Methods: This study presents a complete assessment framework, develops an inventory as an assessment tool, and examines the reliability and validity of the inventory. The study was carried out in three phases: conceptual framework development, inventory development, and an evaluation case study. Fuzzy conjoint analysis was used in the evaluation to deal with subjectivity and ambiguity. As a result of the evaluation, the case study institution was given a patient privacy maturity level between 1 and 5, where 1 is the worst and 5 is the best. Results: The case study evaluated the largest hospital in Turkey, which employs 800 nurses. Half of the nurses, 400, participated in the study. According to the literature, healthcare institutions do not invest enough in protecting patients’ privacy, and the results of the study support this finding. The institution’s maturity level was 2, which is poor. Conclusions: This study measured privacy maturity with many assessment components. The result of the assessment explains to patients and the public whether their data are secure or not. With the implementation of this maturity level, patients have an idea about which institution to choose, and the public can infer the reliability of institutions in terms of patient privacy.
Work-Related Psychosocial Factors and Their Effects on Mental Workload Perception and Body Postures
Authors: Adams Rodrick , Nino Valentina
Published: July 2024

The perception of work is closely linked to body reactions that facilitate task performance. Previous studies have shown that psychosocial work factors significantly impact employee health on both psychological and physical levels, though their cross-sectional designs limit causal interpretations. In this study, participants performed sitting and standing tasks under four different levels of mental workload. The NASA-Task Load Index (NASA-TLX) assessed mental workload perception across six dimensions, while Rapid Entire Body Assessment (REBA) and Rapid Upper Limb Assessment (RULA) scores evaluated body postures for standing and sitting tasks, respectively. This study examined the effects of alarms, distractions, and time constraints—common psychosocial factors in healthcare environments—on human behavior. We compared NASA-TLX scores with corresponding REBA/RULA scores to evaluate how perceived mental workload affects body postures. One-way ANOVA assessed the impact of experimental conditions on response variables, and Pearson correlation analyses explored the relationships between psychosocial factors and these variables. Results indicated that alarm conditions most negatively impacted mental workload perception and body postures. Temporal demand and effort scores were particularly affected by psychosocial factors in both tasks. Gender influenced physical demand and performance scores (higher in females) for the standing task but did not affect REBA and RULA scores. These findings suggest that organizational and psychosocial factors significantly influence healthcare workers’ behavior, health, and patient safety. Further research is needed to evaluate the specific effects of psychosocial factors on both physical and mental workload to understand the relationship between overall task workload and occupational disorders.
An Implementation Evaluation of the Smartphone-Enhanced Visual Inspection with Acetic Acid (SEVIA) Program for Cervical Cancer Prevention in Urban and Rural Tanzania
Authors: Ferguson Alyssa L. , Erwin Erica , Sleeth Jessica , Symonds Nicola , Chard Sidonie , Yuma Safina , Oneko Olola , Macheku Godwin , Andrews Linda , West Nicola , Chelva Melinda , Ginsburg Ophira , Yeates Karen
Published: July 2024

Introduction: The World Health Organization (WHO) recommends visual inspection with acetic acid (VIA) for cervical cancer screening (CCS) in lower-resource settings; however, quality varies widely, and it is difficult to maintain a well-trained cadre of providers. The Smartphone-Enhanced Visual Inspection with Acetic acid (SEVIA) program was designed to offer secure sharing of cervical images and real-time supportive supervision to health care workers, in order to improve the quality and accuracy of visual assessment of the cervix for treatment. The purpose of this evaluation was to document early learnings from patients, providers, and higher-level program stakeholders, on barriers and enablers to program implementation. Methods: From 9 September to 8 December 2016, observational activities and open-ended interviews were conducted with image reviewers (n = 5), providers (n = 17), community mobilizers (n = 14), patients (n = 21), supervisors (n = 4) and implementation partners (n = 5) involved with SEVIA. Sixty-six interviews were conducted at 14 facilities, in all five of the program regions Results SEVIA was found to be a highly regarded tool for the enhancement of CCS services in Northern Tanzania. Acceptability, adoption, appropriateness, feasibility, and coverage of the intervention were highly recognized. It appeared to be an effective means of improving good clinical practice among providers and fit seamlessly into existing roles and processes. Barriers to implementation included network connectivity issues, and community misconceptions and the adoption of CCS more generally. Conclusions: SEVIA is a practical and feasible mobile health intervention and tool that is easily integrated into the National CCS program to enhance the quality of care.
Knowledge and Competence Regarding the Management of Chronic Kidney Disease among Family Medicine Professionals in the Eastern Province of Saudi Arabia: A Cross-Sectional Study
Authors: Almaqhawi Abdullah
Published: July 2024

Diabetes is a significant risk factor for chronic kidney disease (CKD) and a primary cause of global morbidity and mortality, resulting in significant costs to healthcare systems. The management of diabetic CKD in the primary care setting remains an ongoing challenge despite the current best practices in the quality of care. This study evaluated family medicine physicians’ knowledge and confidence regarding managing CKD in the Eastern Province of Saudi Arabia. A self-administered online questionnaire was distributed to physicians through various social media sites and email lists. The largest number of participants reported a full confidence in knowing kidney disease stages, blood pressure targets and the importance of urine albumin–creatinine ratio testing. Overall, 71.8% of physicians reported a high confidence level, followed by 23.9% reporting average and 4.2% reporting low confidence. Being younger and working at PHC were identified as significant predictors of increased confidence. Although most of the physicians reported a high confidence in managing CKD patients, the need for improvement was evident. Age and workplace institutions were the greater contributors to physicians’ confidence. Continuous education among healthcare practitioners is crucial to updating knowledge and providing optimum quality of care among this group of patients.
A Four-Wave Cross-Lagged Study of Exposure to Violent Contexts, Cognitive Distortions, and School Bullying during Adolescence
Authors: Dragone Mirella , Bacchini Dario , Esposito Concetta , Affuso Gaetana , De Angelis Grazia , Stasolla Fabrizio , De Luca Picione Raffaele
Published: July 2024

School bullying represents a widespread expression of violence in the peer context. Guided by the social-ecological model, this study investigated the longitudinal and transactional pathways linking domestic and neighborhood/community violence exposure (through direct victimization and witnessing), self-serving cognitive distortions (CDs), and school bullying perpetration. Furthermore, consistent with the previous literature, we tested the cognitive desensitization process that could develop in response to chronically violent contexts. Two four-wave cross-lagged panel mediation models were tested in a sample of 778 high school students (28.1% males; Mage [Time 1; T1] = 14.20, SD = 0.58). The results showed differential effects of multiple contexts and forms of violence exposure, with domestic violence victimization and community violence witnessing being associated with self-serving CDs and bullying perpetration over time. Moreover, significant associations between CDs and bullying perpetration over time were found, with bidirectional effects for each of these longitudinal patterns. Finally, self-serving CDs significantly mediated the relationships between both domestic violence victimization and community violence witnessing and school bullying perpetration. These findings highlight the need to consider school bullying as a social phenomenon stemming from a complex and bidirectional interplay between individuals and the environments they inhabit, confirming a basic postulate that “violence breeds violence”.
Psychache, Hopelessness, and Suicidal Ideation and Behaviors: A Cross-Sectional Study from China
Authors: Siau Ching Sin , Klonsky E. David , Kõlves Kairi , Huen Jenny Mei Yiu , Chan Caryn Mei Hsien , Fariduddin Muhamad Nur , Ibrahim Norhayati , Tan Yee Kee , Jia Cunxian , Zhang Jie , Lew Bob
Published: July 2024

This study explored the relationship between variables emphasized in the theory’s first step of the three-step theory (3ST)—psychache, hopelessness, and their interaction—to suicide-related variables (i.e., lifetime suicidal ideation and attempt, past-year suicidal ideation, communication of suicidal thoughts, and self-reported future suicide attempt likelihood). Chinese undergraduate students (N = 11,399; mean age = 20.69 ± 1.35) from seven provinces participated in this cross-sectional survey. They answered the Suicidal Behaviors Questionnaire-Revised, Psychache Scale, and Beck Hopelessness Scale. Bivariate and multivariate analyses were used to examine the association between psychache, hopelessness, and hopelessness × psychache interaction on the outcome variables. Bivariate analyses showed that psychache and hopelessness were correlated with suicidal ideation and behaviors. In multiple regression models, the interaction between psychache and hopelessness was significantly associated with past-year suicidal ideation and self-report chances of a future suicide attempt, p < 0.001, though effect sizes for the interaction term were small. The results are broadly consistent with the 3ST’s proposition of how the combination of pain and hopelessness is related to various suicide-related variables. The low prevalence of suicide-related communication should inform future suicide prevention measures by encouraging help-seeking. Psychache as a correlate of the self-reported likelihood of a future attempt could be further investigated.
An Integrated Framework for Landscape Indices’ Calculation with Raster–Vector Integration and Its Application Based on QGIS
Authors: Huang Yaqi , Zheng Minrui , Li Tianle , Xiao Fei , Zheng Xinqi
Published: July 2024

Landscape-index calculation tools play a pivotal role in ecosystem studies and urban-planning research, enabling objective assessments of landscape patterns’ similarities and differences. However, the existing tools encounter limitations, such as the inability to visualize landscape indices spatially and the challenge of computing indices for both vector and raster data simultaneously. Based on the QGIS development platform, this study presents an innovative framework for landscape-index calculation that addresses these limitations. The framework seamlessly integrates both vector and raster data, comprising three main modules: data input, landscape-index calculation, and visualization. In the data-input module, the tool accommodates various data formats, including vector, raster, and tabular data. The landscape indices’ calculation module allows users to select indices at patch, class, and landscape scales. Notably, the framework provides a comprehensive set of 165 indices for vector data and 20 for raster data, empowering users to selectively calculate landscape indices for vector or raster data to their specific needs and leverage the strengths of each data type. Moreover, the landscape-index visualization module enhances spatial visualization capabilities, meeting user demands for an insightful analysis. By addressing these challenges and offering enhanced functionalities, this framework aims to advance landscape indices’ development and foster more comprehensive landscape analyses. And it presents a novel approach for landscape-index development.
Macrophages and HLA-Class II Alleles in Multiple Sclerosis: Insights in Therapeutic Dynamics
Authors: Prapas Petros , Anagnostouli Maria
Published: July 2024

Antigen presentation is a crucial mechanism that drives the T cell-mediated immune response and the development of Multiple Sclerosis (MS). Genetic alterations within the highly variable Major Histocompatibility Complex Class II (MHC II) have been proven to result in significant changes in the molecular basis of antigen presentation and the clinical course of patients with both Adult-Onset MS (AOMS) and Pediatric-Onset MS (POMS). Among the numerous polymorphisms of the Human Leucocyte Antigens (HLA), within MHC II complex, HLA-DRB1*15:01 has been labeled, in Caucasian ethnic groups, as a high-risk allele for MS due to the ability of its structure to increase affinity to Myelin Basic Protein (MBP) epitopes. This characteristic, among others, in the context of the trimolecular complex or immunological synapsis, provides the foundation for autoimmunity triggered by environmental or endogenous factors. As with all professional antigen presenting cells, macrophages are characterized by the expression of MHC II and are often implicated in the formation of MS lesions. Increased presence of M1 macrophages in MS patients has been associated both with progression and onset of the disease, each involving separate but similar mechanisms. In this critical narrative review, we focus on macrophages, discussing how HLA genetic alterations can promote dysregulation of this population’s homeostasis in the periphery and the Central Nervous System (CNS). We also explore the potential interconnection in observed pathological macrophage mechanisms and the function of the diverse structure of HLA alleles in neurodegenerative CNS, seen in MS, by comparing available clinical with molecular data through the prism of HLA-immunogenetics. Finally, we discuss available and experimental pharmacological approaches for MS targeting the trimolecular complex that are based on cell phenotype modulation and HLA genotype involvement and try to reveal fertile ground for the potential development of novel drugs.
Assessment of Concentration KRT6 Proteins in Tumor and Matching Surgical Margin from Patients with Head and Neck Squamous Cell Carcinoma
Authors: Nałęcz Dariusz , Świętek Agata , Hudy Dorota , Wiczkowski Karol , Złotopolska Zofia , Strzelczyk Joanna Katarzyna
Published: July 2024

Head and neck squamous cell carcinomas (HNSCCs) are one of the most frequently detected cancers in the world; not all mechanisms related to the expression of keratin in this type of cancer are known. The aim of this study was to evaluate type II cytokeratins (KRT): KRT6A, KRT6B, and KRT6C protein concentrations in 54 tumor and margin samples of head and neck squamous cell carcinoma (HNSCC). Moreover, we examined a possible association between protein concentration and the clinical and demographic variables. Protein concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher KRT6A protein concentration was found in HNSCC samples compared to surgical margins. An inverse relationship was observed for KRT6B and KRT6C proteins. We showed an association between the KRT6C protein level and clinical parameters T and N in tumor and margin samples. When analyzing the effect of smoking and drinking on KRT6A, KRT6B, and KRT6C levels, we demonstrated a statistically significant difference between regular or occasional tobacco and alcohol habits and patients who do not have any tobacco and alcohol habits in tumor and margin samples. Moreover, we found an association between KRT6B and KRT6C concentration and proliferative index Ki-67 and HPV status in tumor samples. Our results showed that concentrations of KRT6s were different in the tumor and the margin samples and varied in relation to clinical and demographic parameters. We add information to the current knowledge about the role of KRT6s isoforms in HNSCC. We speculate that variations in the studied isoforms of the KRT6 protein could be due to the presence and development of the tumor and its microenvironment. It is important to note that the analyses were performed in tumor and surgical margins and can provide more accurate information on the function in normal and cancer cells and regulation in response to various factors.
Intestinal Epithelial Co-Culture Sensitivity to Pro-Inflammatory Stimuli and Polyphenols Is Medium-Independent
Authors: Haddad Michelle J. , Zuluaga-Arango Juanita , Mathieu Hugo , Barbezier Nicolas , Anton Pauline M.
Published: July 2024

The complexification of in vitro models requires the compatibility of cells with the same medium. Since immune cells are the most sensitive to growth conditions, growing intestinal epithelial cells in their usual medium seems to be necessary. This work was aimed at comparing the sensitivity of these epithelial cells to pro-inflammatory stimuli but also to dietary polyphenols in both DMEM and RPMI-1640 media. Co-cultures of Caco-2 and HT29-MTX cells were grown for 21 days in the two media before their stimulation with a cocktail of TNF-α (20 ng/mL), IL-1β (1 ng/mL), and IFN-γ (10 ng/mL) or with LPS (10 ng/mL) from E. coli (O111:B4). The role of catechins (15 µM), a dietary polyphenol, was evaluated after its incubation with the cells before their stimulation for 6 h. The RPMI-1640 medium did not alter the intensity of the inflammatory response observed with the cytokines. By contrast, LPS failed to stimulate the co-culture in inserts regardless of the medium used. Lastly, catechins were unable to prevent the pro-inflammatory response observed with the cytokines in the two media. The preservation of the response of this model of intestinal epithelium in RPMI-1640 medium is promising when considering its complexification to evaluate the complex cellular crosstalk leading to intestinal homeostasis.
ERK/CREB and p38 MAPK/MMP14 Signaling Pathway Influences Spermatogenesis through Regulating the Expression of Junctional Proteins in Eriocheir sinensis Testis
Authors: Qi Hong-Yu , Zhao Zhan , Wei Bang-Hong , Li Zhen-Fang , Tan Fu-Qing , Yang Wan-Xi
Published: July 2024

The hemolymph–testis barrier (HTB) is a reproduction barrier in Crustacea, guaranteeing the safe and smooth process of spermatogenesis, which is similar to the blood–testis barrier (BTB) in mammals. The MAPK signaling pathway plays an essential role in spermatogenesis and maintenance of the BTB. However, only a few studies have focused on the influence of MAPK on crustacean reproduction. In the present study, we knocked down and inhibited MAPK in Eriocheir sinensis. Increased defects in spermatogenesis were observed, concurrently with a damaged HTB. Further research revealed that es-MMP14 functions downstream of ERK and p38 MAPK and degrades junctional proteins (Pinin and ZO-1); es-CREB functions in the ERK cascade as a transcription factor of ZO-1. In addition, when es-MMP14 and es-CREB were deleted, the defects in HTB and spermatogenesis aligned with abnormalities in the MAPK. However, JNK impacts the integrity of the HTB by changing the distribution of intercellular junctions. In summary, the MAPK signaling pathway maintains HTB integrity and spermatogenesis through es-MMP14 and es-CREB, which provides insights into the evolution of gene function during barrier evolution.
Enhanced Genomic and Transcriptomic Resources for Trichinella pseudospiralis and T. spiralis to Underpin the Discovery of Molecular Differences between Stages and Species
Authors: Korhonen Pasi K. , La Rosa Giuseppe , Sumanam Sunita B. , Gomez Morales Maria Angeles , Ludovisi Alessandra , Pozio Edoardo , Tonanzi Daniele , Chang Bill C. H. , Young Neil D. , Gasser Robin B.
Published: July 2024

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host–parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin—with possible roles in modulating host immune responses and facilitating parasite survival—were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella–host interactions might offer possible avenues for developing new interventions against trichinellosis.
Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome
Authors: Udugampolage Nathasha Samali , Frolova Svetlana , Taurino Jacopo , Pini Alessandro , Martelli Fabio , Voellenkle Christine
Published: July 2024

Marfan syndrome (MFS) is a rare congenital disorder of the connective tissue, leading to thoracic aortic aneurysms (TAA) and dissection, among other complications. Currently, the most efficient strategy to prevent life-threatening dissection is preventive surgery. Periodic imaging applying complex techniques is required to monitor TAA progression and to guide the timing of surgical intervention. Thus, there is an acute demand for non-invasive biomarkers for diagnosis and prognosis, as well as for innovative therapeutic targets of MFS. Unraveling the intricate pathomolecular mechanisms underlying the syndrome is vital to address these needs. High-throughput platforms are particularly well-suited for this purpose, as they enable the integration of different datasets, such as transcriptomic and epigenetic profiles. In this narrative review, we summarize relevant studies investigating changes in both the coding and non-coding transcriptome and epigenome in MFS-induced TAA. The collective findings highlight the implicated pathways, such as TGF-β signaling, extracellular matrix structure, inflammation, and mitochondrial dysfunction. Potential candidates as biomarkers, such as miR-200c, as well as therapeutic targets emerged, like Tfam, associated with mitochondrial respiration, or miR-632, stimulating endothelial-to-mesenchymal transition. While these discoveries are promising, rigorous and extensive validation in large patient cohorts is indispensable to confirm their clinical relevance and therapeutic potential.
Photophysical Characterization and In Vitro Evaluation of α-Mangostin-Loaded HDL Mimetic Nano-Complex in LN-229 Glioblastoma Spheroid Model
Authors: Kapic Ammar , Sabnis Nirupama , Dossou Akpedje S. , Chavez Jose , Ceresa Luca , Gryczynski Zygmunt , Fudala Rafal , Dickerman Rob , Bunnell Bruce A. , Lacko Andras G.
Published: July 2024

Cytotoxic activity has been reported for the xanthone α-mangostin (AMN) against Glioblastoma multiforme (GBM), an aggressive malignant brain cancer with a poor prognosis. Recognizing that AMN’s high degree of hydrophobicity is likely to limit its systemic administration, we formulated AMN using reconstituted high-density lipoprotein (rHDL) nanoparticles. The photophysical characteristics of the formulation, including fluorescence lifetime and steady-state anisotropy, indicated that AMN was successfully incorporated into the rHDL nanoparticles. To our knowledge, this is the first report on the fluorescent characteristics of AMN with an HDL-based drug carrier. Cytotoxicity studies in a 2D culture and 3D spheroid model of LN-229 GBM cells and normal human astrocytes showed an enhanced therapeutic index with the rHDL-AMN formulation compared to the unincorporated AMN and Temozolomide, a standard GBM chemotherapy agent. Furthermore, treatment with the rHDL-AMN facilitated a dose-dependent upregulation of autophagy and reactive oxygen species generation to a greater extent in LN-229 cells compared to astrocytes, indicating the reduced off-target toxicity of this novel formulation. These studies indicate the potential therapeutic benefits to GBM patients via selective targeting using the rHDL-AMN formulation.
Interactions with DNA Models of the Oxaliplatin Analog (cis-1,3-DACH)PtCl2
Authors: Barbanente Alessandra , Papadia Paride , Di Cosola Anna Maria , Pacifico Concetta , Natile Giovanni , Hoeschele James D. , Margiotta Nicola
Published: July 2024

It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand cis-1,3-diaminocyclohexane (cis-1,3-DACH) upon formation, stability, and stereochemistry of the (cis-1,3-DACH)PtG2 and (cis-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5′- and 3′-guanosine monophosphate; d(GpG) = deoxyguanosil(3′-5′)deoxyguanosine). A peculiar feature of the cis-1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane. The (cis-1,3-DACH)Pt(5′GMP)2 and (cis-1,3-DACH)Pt(3′GMP)2 adducts show preference for the ΛHT and ∆HT conformations, respectively (HT stands for Head-to-Tail). Moreover, the increased intensity of the circular dichroism signals in the cis-1,3-DACH derivatives with respect to the analogous cis-(NH3)2 species could be a consequence of the greater bite angle of the cis-1,3-DACH carrier ligand with respect to cis-(NH3)2. Finally, the (cis-1,3-DACH)Pt(d(GpG)) adduct is present in two isomeric forms, each one giving a pair of H8 resonances linked by a NOE cross peak. The two isomers were formed in comparable amounts and had a dominance of the HH conformer but with some contribution of the ΔHT conformer which is related to the HH conformer by having the 3′-G base flipped with respect to the 5′-G residue.
Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment
Authors: Jang Jin Ho , Choi Eunjeong , Kim Taehwa , Yeo Hye Ju , Jeon Doosoo , Kim Yun Seong , Cho Woo Hyun
Published: July 2024

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.
Proteomic Characterization of a 3D HER2+ Breast Cancer Model Reveals the Role of Mitochondrial Complex I in Acquired Resistance to Trastuzumab
Authors: Tapia Ivana J. , Perico Davide , Wolos Virginia J. , Villaverde Marcela S. , Abrigo Marianela , Di Silvestre Dario , Mauri Pierluigi , De Palma Antonella , Fiszman Gabriel L.
Published: July 2024

HER2-targeted therapies, such as Trastuzumab (Tz), have significantly improved the clinical outcomes for patients with HER2+ breast cancer (BC). However, treatment resistance remains a major obstacle. To elucidate functional and metabolic changes associated with acquired resistance, we characterized protein profiles of BC Tz-responder spheroids (RSs) and non-responder spheroids (nRSs) by a proteomic approach. Three-dimensional cultures were generated from the HER2+ human mammary adenocarcinoma cell line BT-474 and a derived resistant cell line. Before and after a 15-day Tz treatment, samples of each condition were collected and analyzed by liquid chromatography–mass spectrometry. The analysis of differentially expressed proteins exhibited the deregulation of energetic metabolism and mitochondrial pathways. A down-regulation of carbohydrate metabolism and up-regulation of mitochondria organization proteins, the tricarboxylic acid cycle, and oxidative phosphorylation, were observed in nRSs. Of note, Complex I-related proteins were increased in this condition and the inhibition by metformin highlighted that their activity is necessary for nRS survival. Furthermore, a correlation analysis showed that overexpression of Complex I proteins NDUFA10 and NDUFS2 was associated with high clinical risk and worse survival for HER2+ BC patients. In conclusion, the non-responder phenotype identified here provides a signature of proteins and related pathways that could lead to therapeutic biomarker investigation.
Association of Perinatal Cardiovascular Features with Angiotensin System Expressions in Maternal Preeclampsia
Authors: Lin I-Chun , Wu Kay L. H. , Cheng Hsin-Hsin , Tsai Ching-Chang , Yu Hong-Ren , Hsu Te-Yao , Tain You-Lin , Huang Li-Tung , Lai Yun-Ju
Published: July 2024

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.
Termite Fungus Comb Polysaccharides Alleviate Hyperglycemia and Hyperlipidemia in Type 2 Diabetic Mice by Regulating Hepatic Glucose/Lipid Metabolism and the Gut Microbiota
Authors: Xiao Haihan , Song Xudong , Wang Peng , Li Weilin , Qin Senhua , Huang Chaofu , Wu Beimin , Jia Bao , Gao Qionghua , Song Ziyi
Published: July 2024

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and dyslipidemia. The termite fungus comb is an integral component of nests of termites, which are a global pest. Termite fungus comb polysaccharides (TFCPs) have been identified to possess antioxidant, anti-aging, and immune-enhancing properties. However, their physicochemical characteristics and their role in fighting diabetes have not been previously reported. In the current study, TFCPs were isolated and structurally characterized. The yield of TFCPs was determined to be 2.76%, and it was found to be composed of a diverse array of polysaccharides with varying molecular weights. The hypoglycemic and hypolipidemic effects of TFCPs, as well as their potential mechanisms of action, were investigated in a T2D mouse model. The results demonstrated that oral administration of TFCPs could alleviate fasting blood glucose levels, insulin resistance, hyperlipidemia, and the dysfunction of pancreatic islets in T2D mice. In terms of mechanisms, the TFCPs enhanced hepatic glycogenesis and glycolysis while inhibiting gluconeogenesis. Additionally, the TFCPs suppressed hepatic de novo lipogenesis and promoted fatty acid oxidation. Furthermore, the TFCPs altered the composition of the gut microbiota in the T2D mice, increasing the abundance of beneficial bacteria such as Allobaculum and Faecalibaculum, while reducing the levels of pathogens like Mailhella and Acetatifactor. Overall, these findings suggest that TFCPs may exert anti-diabetic effects by regulating hepatic glucose and lipid metabolism and the composition of the gut microbiota. These findings suggest that TFCPs can be used as a promising functional ingredient for the prevention and treatment of T2D.
Transcriptomic Analysis Reveals That Excessive Thyroid Hormone Signaling Impairs Phototransduction and Mitochondrial Bioenergetics and Induces Cellular Stress in Mouse Cone Photoreceptors
Authors: Ma Hongwei , Stanford David , Freeman Willard M. , Ding Xi-Qin
Published: July 2024

Thyroid hormone (TH) plays an essential role in cell proliferation, differentiation, and metabolism. Experimental and clinical studies have shown a potential association between TH signaling and retinal degeneration. The suppression of TH signaling protects cone photoreceptors in mouse models of retinal degeneration, whereas excessive TH signaling induces cone degeneration, manifested as reduced light response and a loss of cones. This work investigates the genes/transcriptomic alterations that might be involved in TH-induced cone degeneration in mice using single-cell RNA sequencing (scRNAseq) analysis. One-month-old C57BL/6 mice received triiodothyronine (T3, 20 µg/mL in drinking water) for 4 weeks as a model of hyperthyroidism/excessive TH signaling. At the end of the experiments, retinal cells were dissociated, and cell viability was analyzed before being subjected to scRNAseq. The resulting data were analyzed using the Seurat package and visualized using the Loupe browser. Among 155,866 single cells, we identified 14 cell clusters, representing various retinal cell types, with rod and cone clusters comprising 76% and 4.1% of the total cell population, respectively. Cone cluster transcriptomes demonstrated the most alterations after the T3 treatment, with 450 differentially expressed genes (DEGs), accounting for 38.5% of the total DEGs. Statistically significant changes in the expression of genes in the cone cluster revealed that phototransduction and oxidative phosphorylation were impaired after the T3 treatment, along with mitochondrial dysfunction. A pathway analysis also showed the activation of the sensory neuronal/photoreceptor stress pathways after the T3 treatment. Specifically, the eukaryotic initiation factor-2 signaling pathway and the cAMP response element-binding protein signaling pathway were upregulated. Thus, excessive TH signaling substantially affects cones at the transcriptomic level. The findings from this work provide an insight into how excessive TH signaling induces cone degeneration.
The Protective Effect of Uridine in a Rotenone-Induced Model of Parkinson’s Disease: The Role of the Mitochondrial ATP-Dependent Potassium Channel
Authors: Mironova Galina D. , Mosentsov Alexei A. , Mironov Vasilii V. , Medvedeva Vasilisa P. , Khunderyakova Natalia V. , Pavlik Lyubov L. , Mikheeva Irina B. , Shigaeva Maria I. , Agafonov Alexey V. , Khmil Natalya V. , Belosludtseva Natalia V.
Published: July 2024

The effect of the modulators of the mitochondrial ATP-dependent potassium channel (mitoKATP) on the structural and biochemical alterations in the substantia nigra and brain tissues was studied in a rat model of Parkinson’s disease induced by rotenone. It was found that, in experimental parkinsonism accompanied by characteristic motor deficits, both neurons and the myelin sheath of nerve fibers in the substantia nigra were affected. Changes in energy and ion exchange in brain mitochondria were also revealed. The nucleoside uridine, which is a source for the synthesis of the mitoKATP channel opener uridine diphosphate, was able to dose-dependently decrease behavioral disorders and prevent the death of animals, which occurred for about 50% of animals in the model. Uridine prevented disturbances in redox, energy, and ion exchanges in brain mitochondria, and eliminated alterations in their structure and the myelin sheath in the substantia nigra. Cytochemical examination showed that uridine restored the indicators of oxidative phosphorylation and glycolysis in peripheral blood lymphocytes. The specific blocker of the mitoKATP channel, 5-hydroxydecanoate, eliminated the positive effects of uridine, suggesting that this channel is involved in neuroprotection. Taken together, these findings indicate the promise of using the natural metabolite uridine as a new drug to prevent and, possibly, stop the progression of Parkinson’s disease.
Inhibition of Cancer Stem-like Cells by Curcumin and Other Polyphenol Derivatives in MDA-MB-231 TNBC Cells
Authors: Ros Maria , Riesco-Llach Gerard , Polonio-Alcalá Emma , Morla-Barcelo Pere Miquel , Ruiz-Martínez Santiago , Feliu Lidia , Planas Marta , Puig Teresa
Published: July 2024

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.