bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Frédéric Flachéron’s Paper Negative Process through Experimentation and Specular Reflection FTIR Analysis
Authors: Bulat Elena , Panadero Laura , Murphy Erin , McClelland Arthur
Published: August 2023

Cultural heritage objects present a special set of challenges for chemical analysis. Often micro-sampling or even contacting the object is deemed an unacceptable risk to the object. This study examined if specular reflection FTIR, a non-sampling and non-contact analytical technique, can provide insight into chemical composition of the layered coatings on Frédéric Flachéron’s paper negatives (1848–1852) in the Harrison D. Horblit Collection of Early Photography, in Houghton Library, at Harvard University. Specular reflection FTIR data confirmed the identification of beeswax and sandarac as the transparentizing media on Flachéron’s paper negatives, as previously published by Lee Ann Daffner. However, specular reflection FTIR analysis also indicated that some negatives had additional localized coatings of orange shellac in specific areas of the images. To understand why Flachéron retouched his negatives with orange shellac, modern experimental replications of the paper negative process were performed. Through modern experimentation with the paper negative technique, it was found that Flachéron’s coatings of shellac served as an integral part of his image-altering technique. The color of the orange shellac subtly alters contrast and density, but it does not mask an area the way an opaque watercolor or highly pigmented paint might. The fine adjustments to the negatives with orange shellac were an attempt to perfect the contrast in the print, and better render depth and detail. These discoveries add to a growing body of recent research that points to the historic and art historic importance of negatives and coatings in photography. The specificity with which specular reflection FTIR was able to nondestructively identify the chemical composition of the local coating, and specifically target the analysis on the areas in which it appeared, allowed for an understanding of Flachéron’s use of local coatings as a retouching method rather than a protective coating.
Evaluation of Self-Collected Versus Health Care Professional (HCP)-Performed Sampling and the Potential Impact on the Diagnostic Results of Asymptomatic Sexually Transmitted Infections (STIs) in High-Risk Individuals
Authors: Weidlich Simon , Schellberg Sven , Scholten Stefan , Schneider Jochen , Lee Marcel , Rothe Kathrin , Wantia Nina , Spinner Christoph D. , Noe Sebastian
Published: August 2023

Sexually transmitted infections (STIs) are increasing among men who have sex with men (MSM). Screening can improve the detection and outcome of asymptomatic STIs in high-risk populations. Self-sampling may be a resource-optimized strategy; however, its diagnostic reliability compared to testing by healthcare professionals (HCPs) requires further investigation. In this prospective, multicenter cohort study in a high-income country, asymptomatic MSM with a sexual risk profile for STIs were included. Sequential swabs for STI nucleic acid-based diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were performed after randomization, either through self-sampling or HCP-performed sampling. Baseline demographic information, sexual risk behavior, and acceptance and feedback on self-sampling were recorded using an electronic questionnaire. Out of 236 asymptomatic MSM, 47 individuals (19.9%) tested positive for CT and/or NG through self- or HCP-performed sampling. For CT, the sensitivity was 93.3% for both sampling methods, while for NG, it was 90.0% for self-sampling and 95.0% for HCP-performed sampling. Our study demonstrates that self-sampling for asymptomatic STIs has a comparable diagnostic outcome to HCP-performed sampling, with high acceptance in high-risk MSM.
Wastewater Monitoring for Infectious Disease: Intentional Relationships between Academia, the Private Sector, and Local Health Departments for Public Health Preparedness
Authors: Ram Jeffrey L. , Shuster William , Gable Lance , Turner Carrie L. , Hartrick James , Vasquez Adrian A. , West Nicholas W. , Bahmani Azadeh , David Randy E.
Published: August 2023

The public health emergency caused by the COVID-19 pandemic stimulated stakeholders from diverse disciplines and institutions to establish new collaborations to produce informed public health responses to the disease. Wastewater-based epidemiology for COVID-19 grew quickly during the pandemic and required the rapid implementation of such collaborations. The objective of this article is to describe the challenges and results of new relationships developed in Detroit, MI, USA among a medical school and an engineering college at an academic institution (Wayne State University), the local health department (Detroit Health Department), and an environmental services company (LimnoTech) to utilize markers of the COVID-19 virus, SARS-CoV-2, in wastewater for the goal of managing COVID-19 outbreaks. Our collaborative team resolved questions related to sewershed selection, communication of results, and public health responses and addressed technical challenges that included ground-truthing the sewer maps, overcoming supply chain issues, improving the speed and sensitivity of measurements, and training new personnel to deal with a new disease under pandemic conditions. Recognition of our complementary roles and clear communication among the partners enabled city-wide wastewater data to inform public health responses within a few months of the availability of funding in 2020, and to make improvements in sensitivity and understanding to be made as the pandemic progressed and evolved. As a result, the outbreaks of COVID-19 in Detroit in fall and winter 2021–2022 (corresponding to Delta and Omicron variant outbreaks) were tracked in 20 sewersheds. Data comparing community- and hospital-associated sewersheds indicate a one- to two-week advance warning in the community of subsequent peaks in viral markers in hospital sewersheds. The new institutional relationships impelled by the pandemic provide a good basis for continuing collaborations to utilize wastewater-based human and pathogen data for improving the public health in the future.
Social Processes of Young Adults’ Recovery and Identity Formation during Life-Disruptive Mental Distress—A Meta-Ethnography
Authors: Storm Ida Marie Skou , Mikkelsen Anne Kathrine Kousgaard , Holen Mari , Hybholt Lisbeth , Austin Stephen Fitzgerald , Berring Lene Lauge
Published: August 2023

Young people’s mental health recovery is well-explored in empirical research, yet there is a lack of meta-studies synthesizing the characteristics of young people’s recovery. This meta-ethnography explores young adults’ recovery during life-disruptive experiences of early psychosis or schizophrenia. Based on a systematic literature review search, 11 empirical qualitative studies were included for synthesis. Inspired by young people’s prominent experience of social isolation in the included studies, we applied an interpretive lens of belonging deriving from the sociology of youth. The synthesis presents five themes: (1) expectations of progression in youth in contrast with stagnation during psychosis, (2) feeling isolated, lost and left behind, (3) young adults’ recovery involves belonging with other young people, (4) forming identity positions of growth and disability during psychosis, and the summarizing line of argument, (5) navigating relational complexities in the process of recovery. While suffering from social isolation, young people’s recovery is conceived as getting on with life, like any other young person involving connecting and synchronizing life rhythms with their age peers. Socializing primarily with caring adults entails being stuck in the position of a child, while connecting with young people enables the identity positions of young people. This synthesis can inspire support for young people’s recovery through social inclusion in youth environments.
Practical Preventive Considerations for Reducing the Public Health Burden of Poultry-Related Salmonellosis
Authors: Raut Rabin , Maharjan Pramir , Fouladkhah Aliyar Cyrus
Published: August 2023

With poultry products as one of the leading reservoirs for the pathogen, in a typical year in the United States, it is estimated that over one million individuals contract non-typhoidal Salmonella infections. Foodborne outbreaks associated with Salmonella infections in poultry, thus, continue to remain a significant risk to public health. Moreover, the further emergence of antimicrobial resistance among various serovars of Salmonella is an additional public health concern. Feeding-based strategies (such as use of prebiotics, probiotics, and/or phytobiotics as well as essential oils), non-feeding-based strategies (such as use of bacteriophages, vaccinations, and in ovo strategies), omics tools and surveillance for identifying antibiotic-resistance genes, post-harvest application of antimicrobials, and biosecurity measures at poultry facilities are practical interventions that could reduce the public health burden of salmonellosis and antibiotic resistance associated with poultry products. With the escalating consumption of poultry products around the globe, the fate, prevalence, and transmission of Salmonella in agricultural settings and various poultry-processing facilities are major public health challenges demanding integrated control measures throughout the food chain. Implementation of practical preventive measures discussed in the current study could appreciably reduce the public health burden of foodborne salmonellosis associated with poultry products.
Creatine Kinase Equilibration and ΔGATP over an Extended Range of Physiological Conditions: Implications for Cellular Energetics, Signaling, and Muscle Performance
Authors: Wiseman Robert Woodbury , Brown Caleb Micah , Beck Thomas Wesley , Brault Jeffrey John , Reinoso Tyler Robert , Shi Yun , Chase Prescott Bryant
Published: August 2023

In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK Keq″) over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq″ is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we were able to obtain improved estimates of ΔGATP, necessitating the reinvestigation of previously reported ADP- and ΔGATP-dependent processes. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies and pH is not altered, the maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis around the role of submicromolar ADP in force generation.
Complete De Novo Assembly of Wolbachia Endosymbiont of Frankliniella intonsa
Authors: Zhang Zhijun , Zhang Jiahui , Chen Qizhang , He Jianyun , Li Xiaowei , Wang Yunsheng , Lu Yaobin
Published: August 2023

As an endosymbiont, Wolbachia exerts significant effects on the host, including on reproduction, immunity, and metabolism. However, the study of Wolbachia in Thysanopteran insects, such as flower thrips Frankliniella intonsa, remains limited. Here, we assembled a gap-free looped genome assembly of Wolbachia strain wFI in a length of 1,463,884 bp (GC content 33.80%), using Nanopore long reads and Illumina short reads. The annotation of wFI identified a total of 1838 protein-coding genes (including 85 pseudogenes), 3 ribosomal RNAs (rRNAs), 35 transfer RNAs (tRNAs), and 1 transfer-messenger RNA (tmRNA). Beyond this basic description, we identified mobile genetic elements, such as prophage and insertion sequences (ISs), which make up 17% of the entire wFI genome, as well as genes involved in riboflavin and biotin synthesis and metabolism. This research lays the foundation for understanding the nutritional mutualism between Wolbachia and flower thrips. It also serves as a valuable resource for future studies delving into the intricate interactions between Wolbachia and its host.
Strategies for Engineering of Extracellular Vesicles
Authors: Danilushkina Anna A. , Emene Charles C. , Barlev Nicolai A. , Gomzikova Marina O.
Published: August 2023

Extracellular vesicles (EVs) are membrane vesicles released by cells into the extracellular space. EVs mediate cell-to-cell communication through local and systemic transportation of biomolecules such as DNA, RNA, transcription factors, cytokines, chemokines, enzymes, lipids, and organelles within the human body. EVs gained a particular interest from cancer biology scientists because of their role in the modulation of the tumor microenvironment through delivering bioactive molecules. In this respect, EVs represent an attractive therapeutic target and a means for drug delivery. The advantages of EVs include their biocompatibility, small size, and low immunogenicity. However, there are several limitations that restrict the widespread use of EVs in therapy, namely, their low specificity and payload capacity. Thus, in order to enhance the therapeutic efficacy and delivery specificity, the surface and composition of extracellular vesicles should be modified accordingly. In this review, we describe various approaches to engineering EVs, and further discuss their advantages and disadvantages to promote the application of EVs in clinical practice.
Structural Variations Contribute to the Genetic Etiology of Autism Spectrum Disorder and Language Impairments
Authors: Alibutud Rohan , Hansali Sammy , Cao Xiaolong , Zhou Anbo , Mahaganapathy Vaidhyanathan , Azaro Marco , Gwin Christine , Wilson Sherri , Buyske Steven , Bartlett Christopher W. , Flax Judy F. , Brzustowicz Linda M. , Xing Jinchuan
Published: August 2023

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restrictive interests and/or repetitive behaviors and deficits in social interaction and communication. ASD is a multifactorial disease with a complex polygenic genetic architecture. Its genetic contributing factors are not yet fully understood, especially large structural variations (SVs). In this study, we aimed to assess the contribution of SVs, including copy number variants (CNVs), insertions, deletions, duplications, and mobile element insertions, to ASD and related language impairments in the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Within the cohort, ~77% of the families contain SVs that followed expected segregation or de novo patterns and passed our filtering criteria. These SVs affected 344 brain-expressed genes and can potentially contribute to the genetic etiology of the disorders. Gene Ontology and protein–protein interaction network analysis suggested several clusters of genes in different functional categories, such as neuronal development and histone modification machinery. Genes and biological processes identified in this study contribute to the understanding of ASD and related neurodevelopment disorders.
From Biomarkers to the Molecular Mechanism of Preeclampsia—A Comprehensive Literature Review
Authors: Rybak-Krzyszkowska Magda , Staniczek Jakub , Kondracka Adrianna , Bogusławska Joanna , Kwiatkowski Sebastian , Góra Tomasz , Strus Michał , Górczewski Wojciech
Published: August 2023

Preeclampsia (PE) is a prevalent obstetric illness affecting pregnant women worldwide. This comprehensive literature review aims to examine the role of biomarkers and understand the molecular mechanisms underlying PE. The review encompasses studies on biomarkers for predicting, diagnosing, and monitoring PE, focusing on their molecular mechanisms in maternal blood or urine samples. Past research has advanced our understanding of PE pathogenesis, but the etiology remains unclear. Biomarkers such as PlGF, sFlt-1, PP-13, and PAPP-A have shown promise in risk classification and preventive measures, although challenges exist, including low detection rates and discrepancies in predicting different PE subtypes. Future perspectives highlight the importance of larger prospective studies to explore predictive biomarkers and their molecular mechanisms, improving screening efficacy and distinguishing between early-onset and late-onset PE. Biomarker assessments offer reliable and cost-effective screening methods for early detection, prognosis, and monitoring of PE. Early identification of high-risk women enables timely intervention, preventing adverse outcomes. Further research is needed to validate and optimize biomarker models for accurate prediction and diagnosis, ultimately improving maternal and fetal health outcomes.
PECAM-1/Thrombus Ratio Correlates with Blood Loss during Off-Pump Coronary Artery Bypass Grafting (OPCAB) Surgery: A Preliminary Study
Authors: Bielicka Natalia , Stankiewicz Adrian , Misztal Tomasz , Kocańda Szymon , Chabielska Ewa , Gromotowicz-Popławska Anna
Published: August 2023

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is considered an antiplatelet molecule. Previously, we introduced a new parameter called the PECAM-1/thrombus ratio, which indicates the proportion of PECAM-1 in the thrombus and provides a precise description of human platelet activity (in vitro). The aim of this study was to determine whether the PECAM-1/thrombus ratio could serve as a predictive factor for bleeding events during off-pump coronary artery bypass grafting (OPCAB). To achieve this, we collected blood samples from 20 patients scheduled to undergo OPCAB surgery. We assessed the PECAM-1/thrombus ratio by evaluating thrombus formation on collagen fibers under flow conditions. Subsequently, we compared the ability of the PECAM-1/thrombus ratio in predicting bleeding risk with other methods that evaluate hemostasis activity. These methods included assessing platelet P-selectin secretion, platelet exposure of phosphatidylserine, plasma coagulation and fibrinolysis system activity, and thrombus formation using the T-TAS assay. Our findings revealed a positive correlation between the PECAM-1/thrombus ratio and the amount of blood component units transfused (BCUT) during the OPCAB surgery. Furthermore, BCUT did not show any significant correlation with other measured hemostasis parameters. This preliminary study suggests that the PECAM-1/thrombus ratio might be a good predictor of bleeding risk during the OPCAB procedure.
The Potential Use of THP-1, a Monocytic Leukemia Cell Line, to Predict Immune-Suppressive Potency of Human Bone-Marrow Stromal Cells (BMSCs) In Vitro: A Pilot Study
Authors: Ren Jiaqiang , Szombath Gergely , Vitale-Cross Lynn , Stroncek David F. , Robey Pamela G. , Hajdara Anna , Szalayova Ildiko , Mayer Balazs , Martin Daniel , Mezey Eva , Nemeth Krisztian
Published: August 2023

Adoptive transfer of cultured BMSCs was shown to be immune-suppressive in various inflammatory settings. Many factors play a role in the process, but no master regulator of BMSC-driven immunomodulation was identified. Consequently, an assay that might predict BMSC product efficacy is still unavailable. Below, we show that BMSC donor variability can be monitored by IL-10 production of monocytes/macrophages using THP-1 cells (immortalized monocytic leukemia cells) co-cultured with BMSCs. Using a mixed lymphocyte reaction (MLR) assay, we also compared the ability of the different donor BMSCs to suppress T-cell proliferation, another measure of their immune-suppressive ability. We found that the BMSCs from a donor that induced the most IL-10 production were also the most efficient in suppressing T-cell proliferation. Transcriptome studies showed that the most potent BMSC batch also had higher expression of several known key immunomodulatory molecules such as hepatocyte growth factor (HGF), PDL1, and numerous members of the PGE2 pathway, including PTGS1 and TLR4. Multiplex ELISA experiments revealed higher expression of HGF and IL6 by the most potent BMSC donor. Based on these findings, we propose that THP-1 cells may be used to assess BMSC immunosuppressive activity as a product characterization assay.
Activated Expression of Rice DMR6-like Gene OsS3H Partially Explores the Susceptibility to Bacterial Leaf Streak Mediated by Knock-Out OsF3H04g
Authors: Wu Tao , Bi Yunya , Yu Yue , Zhou Zhou , Yuan Bin , Ding Xinhua , Zhang Qingxia , Chen Xiangsong , Yang Hong , Liu Haifeng , Chu Zhaohui
Published: August 2023

Downy Mildew Resistance 6-like (DMR6-like) genes are identified as salicylic acid (SA) hydroxylases and negative regulators of plant immunity. Previously, we identified two rice DMR6-like genes, OsF3H03g, and OsF3H04g, that act as susceptible targets of transcription activator-like effectors (TALEs) from Xanthomonas oryzae pv. oryzicola (Xoc), which causes bacterial leaf streak (BLS) in rice. Furthermore, all four homologs of rice DMR6-like proteins were identified to predominantly carry the enzyme activity of SA 5-hydroxylase (S5H), negatively regulate rice broad-spectrum resistance, and cause the loss of function of these OsDMR6s, leading to increased resistance to rice blast and bacterial blight (BB). Here, we curiously found that an OsF3H04g knock-out mutant created by T-DNA insertion, osf3h04g, was remarkedly susceptible to BLS and BB and showed an extreme reduction in SA content. OsF3H04g knock-out rice lines produced by gene-editing were mildly susceptible to BLS and reduced content of SA. To explore the susceptibility mechanism in OsF3H04g loss-of-function rice lines, transcriptome sequencing revealed that another homolog, OsS3H, had induced expression in the loss-of-function OsF3H04g rice lines. Furthermore, we confirmed that a great induction of OsS3H downstream and genomically adjacent to OsF3H04g in osf3h04g was primarily related to the inserted T-DNA carrying quadruple enhancer elements of 35S, while a slight induction was caused by an unknown mechanism in gene-editing lines. Then, we found that the overexpression of OsS3H increased rice susceptibility to BLS, while gene-editing mediated the loss-of-function OsS3H enhanced rice resistance to BLS. However, the knock-out of both OsF3H04g and OsS3H by gene-editing only neutralized rice resistance to BLS. Thus, we concluded that the knock-out of OsF3H04g activated the expression of the OsS3H, partially participating in the susceptibility to BLS in rice.
NLRC5 Deficiency Reduces LPS-Induced Microglial Activation via Inhibition of NF-κB Signaling and Ameliorates Mice’s Depressive-like Behavior
Authors: Sun Chen , Shen Yuqing , Liu Piaopiao , Shen Yi , Hu Yue , Li Ping , Zhang Ying , Miao Fengqin , Zhang Jianqiong
Published: August 2023

Microglia are believed to be the key immune effectors of the central immune microenvironment, and their dysregulation is associated with neuroinflammation and mood disorders. Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain-containing five (NLRC5) is a new member of the Nod-like receptor family. Recently, NLRC5 has been reported to be expressed by microglia. Nonetheless, the exact roles of NLRC5 in microglial activation and its function in depression have not been investigated yet. Herein, we found that reducing NLRC5 decreased lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in primary cultured microglia and microglial cell lines but not in bone marrow-derived macrophages (BMDMs). In more detail, reducing NLRC5 diminished the secretion of LPS-induced cytokines by attenuating IKKα/β phosphorylation and inhibiting NF-κB signaling. Moreover, the expression of Nlrc5 in the hippocampus of LPS- or chronic unpredictable mild stress (CUMS)-induced depressive mice was increased. In line with the in vitro findings, Nlrc5 deficiency inhibited microglial activation in the mouse hippocampus and improved LPS- or CUMS-induced depressive-like behaviors. In summary, we demonstrated the critical role of NLRC5 in LPS-induced microglial activation and LPS- or CUMS-induced depressive mouse models.
Korean Red Ginseng Prevents the Deterioration of Lung and Brain Function in Chronic PM2.5-Exposed Mice by Regulating Systemic Inflammation
Authors: Kim Ju Hui , Kim Jong Min , Lee Hyo Lim , Go Min Ji , Kim Tae Yoon , Joo Seung Gyum , Lee Han Su , Heo Ho Jin
Published: August 2023

This study was conducted to confirm the effects of Korean red ginseng on lung and brain dysfunction in a BALB/c mice model exposed to particulate matter (PM)2.5 for 12 weeks. Learning and cognitive abilities were assessed with Y-maze, passive avoidance, and Morris water maze tests. To evaluate the ameliorating effect of red ginseng extract (RGE), the antioxidant system and mitochondrial function were investigated. The administration of RGE protected lung and brain impairment by regulating the antioxidant system and mitochondrial functions damaged by PM2.5-induced toxicity. Moreover, RGE prevented pulmonary fibrosis by regulating the transforming growth factor beta 1 (TGF-β1) pathway. RGE attenuated PM2.5-induced pulmonary and cognitive dysfunction by regulating systemic inflammation and apoptosis via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/c-Jun N-terminal kinases (JNK) pathway. In conclusion, RGE might be a potential material that can regulate chronic PM2.5-induced lung and brain cognitive dysfunction.
miRNAs Epigenetic Tuning of Wall Remodeling in the Early Phase after Myocardial Infarction: A Novel Epidrug Approach
Authors: Salvatori Francesca , D’Aversa Elisabetta , Serino Maria Luisa , Singh Ajay Vikram , Secchiero Paola , Zauli Giorgio , Tisato Veronica , Gemmati Donato
Published: August 2023

Myocardial infarction (MI) is one of the leading causes of death in Western countries. An early diagnosis decreases subsequent severe complications such as wall remodeling or heart failure and improves treatments and interventions. Novel therapeutic targets have been recognized and, together with the development of direct and indirect epidrugs, the role of non-coding RNAs (ncRNAs) yields great expectancy. ncRNAs are a group of RNAs not translated into a product and, among them, microRNAs (miRNAs) are the most investigated subgroup since they are involved in several pathological processes related to MI and post-MI phases such as inflammation, apoptosis, angiogenesis, and fibrosis. These processes and pathways are finely tuned by miRNAs via complex mechanisms. We are at the beginning of the investigation and the main paths are still underexplored. In this review, we provide a comprehensive discussion of the recent findings on epigenetic changes involved in the first phases after MI as well as on the role of the several miRNAs. We focused on miRNAs function and on their relationship with key molecules and cells involved in healing processes after an ischemic accident, while also giving insight into the discrepancy between males and females in the prognosis of cardiovascular diseases.
The Bidirectional Interplay of α-Synuclein with Lipids in the Central Nervous System and Its Implications for the Pathogenesis of Parkinson’s Disease
Authors: Battis Kristina , Xiang Wei , Winkler Jürgen
Published: August 2023

The alteration and aggregation of alpha-synuclein (α-syn) play a crucial role in neurodegenerative diseases collectively termed as synucleinopathies, including Parkinson’s disease (PD). The bidirectional interaction of α-syn with lipids and biomembranes impacts not only α-syn aggregation but also lipid homeostasis. Indeed, lipid composition and metabolism are severely perturbed in PD. One explanation for lipid-associated alterations may involve structural changes in α-syn, caused, for example, by missense mutations in the lipid-binding region of α-syn as well as post-translational modifications such as phosphorylation, acetylation, nitration, ubiquitination, truncation, glycosylation, and glycation. Notably, different strategies targeting the α-syn-lipid interaction have been identified and are able to reduce α-syn pathology. These approaches include the modulation of post-translational modifications aiming to reduce the aggregation of α-syn and modify its binding properties to lipid membranes. Furthermore, targeting enzymes involved in various steps of lipid metabolism and exploring the neuroprotective potential of lipids themselves have emerged as novel therapeutic approaches. Taken together, this review focuses on the bidirectional crosstalk of α-syn and lipids and how alterations of this interaction affect PD and thereby open a window for therapeutic interventions.
Metabolic Imbalances and Bone Remodeling Agents in Adolescent Idiopathic Scoliosis: A Study in Postmenarcheal Girls
Authors: Danielewicz Anna , Wójciak Magdalena , Sowa Ireneusz , Kusz Monika , Wessely-Szponder Joanna , Dresler Sławomir , Latalski Michał
Published: August 2023

The causes and mechanisms underlying adolescent idiopathic scoliosis (AIS) remain unclear, and the available information regarding metabolic imbalances in AIS is still insufficient. This investigation aimed to evaluate the concentrations of specific bone remodeling-related agents in postmenarcheal girls diagnosed with AIS. The study encompassed thirty-six scoliosis patients and eighteen age-matched healthy individuals assigned to the control group. The patients underwent clinical and radiological examinations to assess the degree of the spinal deformity, type of curvature, and skeletal maturity. Blood and urine samples were collected from all participants and serological markers were measured using an enzyme-linked immunosorbent assay. Our study results demonstrated that the balance of phosphate–calcium and parathormone levels seems normal in individuals with AIS. Furthermore, no statistically significant differences were observed in the content of Klotho protein, osteocalcin, osteoprotegerin, C-terminal telopeptide of type I collagen (CTX), sclerostin, and alkaline phosphatase. Nevertheless, the serum levels of vitamin D (25-OH-D) were lowered, while N-terminal propeptide of type I procollagen (PINP), and fibroblast growth factor-23 (FGF23) were increased in the AIS group, with p-values of 0.044, 0.001, and 0.022, respectively. This finding indicates the potential involvement of these factors in the progression of AIS, which necessitates further studies to uncover the fundamental mechanisms underlying idiopathic scoliosis.
Circulating miRNA Expression Is Inversely Correlated with Tumor Tissue or Sentinel Lymph Nodes in Estrogen Receptor-Positive Early Breast Cancer Patients
Authors: Escuin Daniel , López-Vilaró Laura , Bell Olga , Mora Josefina , García-Valdecasas Bárbara , Moral Antonio , Clos Montserrat , Boronat Laia , Arqueros Cristina , Barnadas Agustí
Published: August 2023

The deregulation of microRNAs (miRNAs) is associated with the various steps of the metastatic process. In addition, circulating miRNAs are remarkably stable in peripheral blood, making them ideal noninvasive biomarkers for disease diagnosis. Here, we performed a proof-of-principle study to determine whether tumor-tissue-derived miRNAs are traceable to plasma in ER-positive early breast cancer patients. We performed RNA-sequencing on 30 patients for whom plasma, sentinel lymph nodes (SLNs) and tumor tissue were available. We carried out differential expression, gene ontology and enrichment analyses. Our results show that circulating miRNAs are inversely expressed compared with tumor tissue or SLNs obtained from the same patients. Our differential expression analysis shows the overall downregulation of circulating miRNAs. However, the expression of miR-643a-3p and miR-223 was up-regulated in patients with positive SLNs. Furthermore, gene ontology analysis showed the significant enrichment of biological processes associated with the regulation of epithelial cell proliferation and transcriptional regulation commonly involved in the promotion of metastases. Our results suggest the potential role of several circulating miRNAs as surrogate markers of lymph node metastases in early breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant miRNAs and to validate our results in a larger cohort of patients.
Platelets Rich Plasma Increases Antioxidant Defenses of Tenocytes via Nrf2 Signal Pathway
Authors: Tognoloni Alessia , Bartolini Desiree , Pepe Marco , Di Meo Antonio , Porcellato Ilaria , Guidoni Kubra , Galli Francesco , Chiaradia Elisabetta
Published: August 2023

Tendinopathies are common disabling conditions in equine and human athletes. The etiology is still unclear, although reactive oxygen species (ROS) and oxidative stress (OS) seem to play a crucial role. In addition, OS has been implicated in the failure of tendon lesion repair. Platelet-rich plasma (PRP) is rich in growth factors that promote tissue regeneration. This is a promising therapeutic approach in tendon injury. Moreover, growing evidence has been attributed to PRP antioxidant effects that can sustain tissue healing. In this study, the potential antioxidant effects of PRP in tenocytes exposed to oxidative stress were investigated. The results demonstrated that PRP reduces protein and lipid oxidative damage and protects tenocytes from OS-induced cell death. The results also showed that PRP was able to increase nuclear levels of redox-dependent transcription factor Nrf2 and to induce some antioxidant/phase II detoxifying enzymes (superoxide dismutase 2, catalase, heme oxygenase 1, NAD(P)H oxidoreductase quinone-1, glutamate cysteine ligase catalytic subunit and glutathione, S-transferase). Moreover, PRP also increased the enzymatic activity of catalase and glutathione S-transferase. In conclusion, this study suggests that PRP could activate various cellular signaling pathways, including the Nrf2 pathway, for the restoration of tenocyte homeostasis and to promote tendon regeneration and repair following tendon injuries.
Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells
Authors: Al-Marsoummi Sarmad , Mehus Aaron A. , Shrestha Swojani , Rice Rayna , Rossow Brooke , Somji Seema , Garrett Scott H. , Sens Donald A.
Published: August 2023

Kidney progenitor cells, although rare and dispersed, play a key role in the repair of renal tubules after acute kidney damage. However, understanding these cells has been challenging due to the limited access to primary renal tissues and the absence of immortalized cells to model kidney progenitors. Previously, our laboratory utilized the renal proximal tubular epithelial cell line, RPTEC/TERT1, and the flow cytometry technique to sort and establish a kidney progenitor cell model called Human Renal Tubular Precursor TERT (HRTPT) which expresses CD133 and CD24 and exhibits the characteristics of kidney progenitors, such as self-renewal capacity and multi-potential differentiation. In addition, a separate cell line was established, named Human Renal Epithelial Cell 24 TERT (HREC24T), which lacks CD133 expression and shows no progenitor features. To further characterize HRTPT CD133+CD24+ progenitor cells, we performed proteomic profiling which showed high proteasomal expression in HRTPT kidney progenitor cells. RT-qPCR, Western blot, and flow cytometry analysis showed that HRTPT cells possess higher proteasomal expression and activity compared to HREC24T non-progenitor cells. Importantly, inhibition of the proteasomes with bortezomib reduced the expression of progenitor markers and obliterated the potential for self-renewal and differentiation of HRTPT progenitor cells. In conclusion, proteasomes are critical in preserving progenitor markers expression and self-renewal capacity in HRTPT kidney progenitors.
Underlying Molecular Mechanism and Construction of a miRNA-Gene Network in Idiopathic Pulmonary Fibrosis by Bioinformatics
Authors: Zheng Shuping , Zhang Yan , Hou Yangfan , Li Hongxin , He Jin , Zhao Hongyan , Sun Xiuzhen , Liu Yun
Published: August 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease, but its pathogenesis is still unclear. Bioinformatics methods were used to explore the differentially expressed genes (DEGs) and to elucidate the pathogenesis of IPF at the genetic level. The microarray datasets GSE110147 and GSE53845 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using GEO2R to obtain the DEGs. The DEGs were further analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment using the DAVID database. Then, using the STRING database and Cytoscape, a protein–protein interaction (PPI) network was created and the hub genes were selected. In addition, lung tissue from a mouse model was validated. Lastly, the network between the target microRNAs (miRNAs) and the hub genes was constructed with NetworkAnalyst. A summary of 240 genes were identified as DEGs, and functional analysis highlighted their role in cell adhesion molecules and ECM–receptor interactions in IPF. In addition, eight hub genes were selected. Four of these hub genes (VCAM1, CDH2, SPP1, and POSTN) were screened for animal validation. The IHC and RT-qPCR of lung tissue from a mouse model confirmed the results above. Then, miR-181b-5p, miR-4262, and miR-155-5p were predicted as possible key miRNAs. Eight hub genes may play a key role in the development of IPF. Four of the hub genes were validated in animal experiments. MiR-181b-5p, miR-4262, and miR-155-5p may be involved in the pathophysiological processes of IPF by interacting with hub genes.
Natural Inhibitors of Amyloid Aggregation
Authors: Tortora Paolo , Aprile Francesco A.
Published: August 2023

Amyloid aggregates are diverse proteinaceous assemblies, including one or more protein species, wherein the molecules interact according to characteristic patterns [...]
Inhibition of Urban Particulate Matter-Induced Airway Inflammation by RIPK3 through the Regulation of Tight Junction Protein Production
Authors: Park Sun-Hee , Lee Hyun-Chae , Jeong Hye Min , Lee Jeong-Sang , Cha Hee-Jae , Kim Cheol Hong , Kim Jeongtae , Song Kyoung Seob
Published: August 2023

Urban particulate matter (UPM) is a high-hazard cause of various diseases in humans, including in the respiratory tract, skin, heart, and even brain. Unfortunately, there is no established treatment for the damage caused by UPM in the respiratory epithelium. In addition, although RIPK3 is known to induce necroptosis, its intracellular role as a negative regulator in human lungs and bronchial epithelia remains unclear. Here, the endogenous expression of RIPK3 was significantly decreased 6 h after exposure to UPM. In RIPK3-ovexpressed cells, RIPK3 was not moved to the cytoplasm from the nucleus. Interestingly, the overexpression of RIPK3 dramatically decreased TEER and F-actin formation. Its overexpression also decreased the expression of genes for pro-inflammatory cytokines (IL-6 and IL-8) and tight junctions (ZO-1, -2, -3, E-cadherin, and claudin) during UPM-induced airway inflammation. Importantly, overexpression of RIPK3 inhibited the UPM-induced ROS production by inhibiting the activation of iNOS and eNOS and by regulating mitochondrial fission processing. In addition, UPM-induced activation of the iκB and NF-κB signaling pathways was dramatically decreased by RIPK3, and the expression of pro-inflammatory cytokines was decreased by inhibiting the iκB signaling pathway. Our data indicated that RIPK3 is essential for the UPM-induced inflammatory microenvironment to maintain homeostasis. Therefore, we suggest that RIPK3 is a potential therapeutic candidate for UPM-induced pulmonary inflammation.
Relapse/Refractory Paediatric B-ALL Case with CD19− Phenotype Switching Indicating the Importance of Appropriate Diagnostic Approach and Targeted Treatment Adjustment—Case Report
Authors: Prażmo Anna , Jawoszek Patryk , Styka Borys , Lejman Monika , Zaucha-Prażmo Agnieszka
Published: August 2023

The case reported presents a rare CD19− phenotype shift of an acute lymphoblastic leukaemia clone during relapse/refractory ALL in a paediatric patient. We explore possible reasons for the promotion of CD19-negative cell selection, including discrete mutations and anti-CD19 treatment, which is gaining importance as targeted therapies such as blinatumomab enter standard treatment protocols. A 9-year-old male patient was diagnosed with B lymphocyte acute lymphoblastic leukaemia. Initial standard genetic analysis did not show significant chromosomal aberrations, and the patient underwent chemotherapy in line with the intermediate-risk protocol. After initially achieving remission, the disease relapsed, and the patient required hematopoietic stem cell transplantation (HSCT). In-depth retrospective microarray analysis performed at this point revealed additional risk factors, particularly a loss of function TP53 V173L mutation. A second recurrence was diagnosed which prompted targeted treatment application (blinatumomab) and subsequent HSCT. The third leukemic relapse, diagnosed shortly after the second HSCT, limited treatment options to last-resort CAR T-cell therapy in Germany. Subsequent immunophenotyping revealed insufficient CD19 expression by ALL clones and disqualified the patient from treatment. The patient died in October 2019 from disease progression. The case highlights the importance of in-depth molecular diagnostics and monitoring of relapse/recurrent ALL cases to identify and manage risk factors during treatment.
Comparative Study of the Efficacy of EHO-85, a Hydrogel Containing Olive Tree (Olea europaea) Leaf Extract, in Skin Wound Healing
Authors: Torrecillas-Baena Bárbara , Camacho-Cardenosa Marta , Carmona-Luque María Dolores , Dorado Gabriel , Berenguer-Pérez Miriam , Quesada-Gómez José Manuel , Gálvez-Moreno María Ángeles , Casado-Díaz Antonio
Published: August 2023

Olive tree (Olea europaea) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort (Centella asiatica), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.
High-Tech Methods of Cytokine Imbalance Correction in Intervertebral Disc Degeneration
Authors: Shnayder Natalia A. , Ashhotov Azamat V. , Trefilova Vera V. , Novitsky Maxim A. , Medvedev German V. , Petrova Marina M. , Narodova Ekaterina A. , Kaskaeva Daria S. , Chumakova Galina A. , Garganeeva Natalia P. , Lareva Natalia V. , Al-Zamil Mustafa , Asadullin Azat R. , Nasyrova Regina F.
Published: August 2023

An important mechanism for the development of intervertebral disc degeneration (IDD) is an imbalance between anti-inflammatory and pro-inflammatory cytokines. Therapeutic and non-therapeutic approaches for cytokine imbalance correction in IDD either do not give the expected result, or give a short period of time. This explains the relevance of high-tech medical care, which is part of specialized care and includes the use of new resource-intensive methods of treatment with proven effectiveness. The aim of the review is to update knowledge about new high-tech methods based on cytokine imbalance correction in IDD. It demonstrates promise of new approaches to IDD management in patients resistant to previously used therapies, including: cell therapy (stem cell implantation, implantation of autologous cultured cells, and tissue engineering); genetic technologies (gene modifications, microRNA, and molecular inducers of IDD); technologies for influencing the inflammatory cascade in intervertebral discs mediated by abnormal activation of inflammasomes; senolytics; exosomal therapy; and other factors (hypoxia-induced factors; lysyl oxidase; corticostatin; etc.).
Theoretical Models for Acceptance of Human Implantable Technologies: A Narrative Review
Authors: Chaudhry Beenish Moalla , Shafeie Shekufeh , Mohamed Mona
Published: August 2023

Theoretical models play a vital role in understanding the barriers and facilitators for the acceptance or rejection of emerging technologies. We conducted a narrative review of theoretical models predicting acceptance and adoption of human enhancement embeddable technologies to assess how well those models have studied unique attributes and qualities of embeddables and to identify gaps in the literature. Our broad search across multiple databases and Google Scholar identified 16 relevant articles published since 2016. We discovered that three main theoretical models: the technology acceptance model (TAM), unified theory of acceptance and use of technology (UTAUT), and cognitive–affective–normative (CAN) model have been consistently used and refined to explain the acceptance of human enhancement embeddable technology. Psychological constructs such as self-efficacy, motivation, self-determination, and demographic factors were also explored as mediating and moderating variables. Based on our analysis, we collated the verified determinants into a comprehensive model, modifying the CAN model. We also identified gaps in the literature and recommended a further exploration of design elements and psychological constructs. Additionally, we suggest investigating other models such as the matching person and technology model (MPTM), the hedonic-motivation system adoption model (HMSAM), and the value-based adoption model (VAM) to provide a more nuanced understanding of embeddable technologies’ adoption. Our study not only synthesizes the current state of research but also provides a robust framework for future investigations. By offering insights into the complex interplay of factors influencing the adoption of embeddable technologies, we contribute to the development of more effective strategies for design, implementation, and acceptance, thereby paving the way for the successful integration of these technologies into everyday life.