bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing Patterns of Nature Contact Associated with Well-Being: An Exploratory Cluster Analysis
Authors: Bressane Adriano , Pinto Joao Pedro da Cunha , Medeiros Líliam César de Castro
Published: June 2024

Statement of Problem: Progressive urbanization has reduced human interactions with nature, raising concerns about its impact on mental well-being. Previous research has often focused on specific aspects of nature contact, neglecting its multifaceted dimensions and their effects on mental health, particularly in developing countries. Research Gap: There is a scarcity of studies exploring the comprehensive dimensions of nature contact, such as frequency, duration, intensity, and space naturalness, and their correlation with mental well-being in developing countries’ urban settings. Purpose: This study aims to identify patterns of nature contact related to mental well-being in metropolitan areas of Brazil using exploratory cluster analysis, bridging the existing knowledge gap and informing targeted interventions to enhance mental health through nature contact. Method: An online survey collected data from 2136 participants in Brazil’s metropolitan areas, focusing on their nature interaction patterns and mental health status using the Depression Anxiety and Stress Scale (DASS-21), hierarchical clustering with p-values via multiscale bootstrap resampling, and analysis of variance. Results and Conclusions: Three distinct groups were identified, showing varied patterns of nature contact and demographic profiles. Greater and more frequent nature contact was associated with lower levels of depression, anxiety, and stress. These findings suggest a beneficial relationship between nature contact and mental well-being. Practical Implications: The results underline the importance of urban planning and public health policies that facilitate access to natural spaces, highlighting socioeconomic factors as significant barriers to this access. Future Directions: Further research should explore causal relationships and consider the specific realities and challenges faced by residents of developing nations.
The Long-Term Effect of Weight Loss on the Prevention of Progression to Cirrhosis among Patients with Obesity and MASH-Related F3 Liver Fibrosis
Authors: Niu Jiafei , Al-Yaman Wael , Pinyopornpanish Kanokwan , Park Ji Seok , Salazar Miguel , Xiao Huijun , Bena James , Lyu Ruishen , Flocco Gianina , Junna Shilpa R. , Adhami Talal , Sims Omar T. , Wakim-Fleming Jamile
Published: June 2024

This multi-center retrospective study examined the effect of weight loss on the prevention of progression to cirrhosis in a sample exclusively composed of patients with obesity and MASH-related F3 liver fibrosis. Adult patients with obesity and biopsy-confirmed MASH-related F3 liver fibrosis (n = 101) from two liver transplant centers in the US were included in the study. A higher proportion of patients who did not progress to cirrhosis achieved >5% weight loss at follow-up (59% vs. 30%, p = 0.045). In multivariable analysis, patients with >5% weight loss at follow-up had a lower hazard of developing cirrhosis compared to patients with no weight loss or weight gain (HR: 0.29, 95%, CI: 0.08–0.96); whereas, diabetes (HR: 3.24, 95%, CI: 1.21–8.67) and higher LDL levels (HR: 1.02, 95%, CI: 1.01–1.04) were associated with higher hazards of progression to cirrhosis. Weight loss >5% has the potential to prevent disease progression to cirrhosis in patients with obesity and MASH-related F3 liver fibrosis. The realization of this benefit requires weight loss maintenance longer than one year. Larger prospective studies are needed to determine how weight loss impacts other patient-centered outcomes such as mortality, hepatic decompensation, and hepatocellular carcinoma in patients with obesity and MASH-related F3 liver fibrosis.
Understanding Professionals’ Knowledge Regarding Factors Influencing Changes in Attitudes toward Female Genital Mutilation/Cutting in Post-Migration Communities in Geneva, Switzerland
Authors: Salah Nasteha , Cantoreggi Nicola , Petignat Patrick , Abdulcadir Jasmine
Published: June 2024

Female genital mutilation or cutting (FGM/C) is a practice involving the partial or complete removal of the external female genitalia for non-medical reasons. To facilitate attitude changes, the ecological model of behavior change considers multiple levels of influence and their relationships with environmental and behavioral factors. The combined effects of migration and cultural adaptation result in a transformative process that leads to decreased support for FGM/C. This qualitative study aimed to gain knowledge from FGM/C field professionals regarding the factors promoting behavioral changes in migrant communities in Geneva, Switzerland. Between September and October 2023, we conducted semi-structured interviews using a reflexive thematic analysis. Our qualitative research is reported in accordance with the COREQ criteria. A data analysis was performed using NVivo 14 software. Four influential dimensions were identified, each with associated factors. The first dimension, the social level, includes (1) the impact and implementation of anti-FGM/C laws. The second dimension, the community level, encompasses four factors such as (2) religion, (3) a multifaceted examination of social aspects, (4) navigating language barriers and raising awareness, and (5) cultural adaptation processes. The third dimension, the interpersonal level, includes factors such as (6) changing views on the marriage prerequisite. Finally, the fourth dimension, the personal level, is associated with (7) women’s experiences and perspectives regarding FGM/C. The findings highlight seven environmental factors, both within and across dimensions of the ecological model, that interact with human behavior to enable an adaptive cultural process. This process influences changes in attitudes and behaviors regarding FGM/C.
Impact of a Nyakaza Move-for-Health Intervention Programme among Adolescents in a Resource-Constrained South African Community
Authors: Zimu Patrick Mkhanyiseli , van Heerden Hendrik Johannes , Grace Jeanne Martin
Published: June 2024

Adolescents in resource-constrained environments face increasing sedentary lifestyles and obesity rates, necessitating effective interventions for promoting physical activity and combating non-communicable diseases. This study evaluates the impact of a 12 week Nyakaza Move-for-Health intervention on physical activity, anthropometry, cardiorespiratory fitness, and behaviour change among adolescents in KwaZulu-Natal, South Africa. One hundred twenty-eight adolescents participated, with assessments including self-reported physical activity, anthropometric indices, and cardiorespiratory fitness measures. The intervention significantly increased physical activity levels. The treatment group’s mean score was 2.2 (0.4) at baseline and 2.6 (0.4) (F (14, 79) = 4.884, p = <0.001, η2 = 0.156) at the endline. The body mass index decreased (mean = 22.4 (4.6) at baseline and 21.9 (4.2) at endline; p = 0.025, partial eta squared = 0.025, η2 = 0.004). The intervention programme significantly affected the WHR (mean = 0.80 (0.10) at baseline and 0.76 (0.9) at endline; p < 0.001, partial eta squared = 0.327, η2 = 0.100) and the predicted maximal oxygen uptake (VO2 max) for the treatment group (mean = 42.4 (8.7) at baseline and mean = 43.6 (8.7) at endline; p < 0.711, partial eta squared = 0.017, η2 = 0.033). Focus group discussions indicated shifts in knowledge, attitudes, and motivation towards physical activity. Power analysis revealed strong observed power (PA: 0.983, BMI: 0.098, WHR: 0.887), indicating the robustness of the intervention’s effects. These findings underscore the effectiveness of the intervention in improving physical health outcomes. It is recommended that longitudinal studies be conducted to assess the long-term sustainability and impact of such interventions on adolescents’ health outcomes, thereby informing the development of comprehensive public health policies and programmes to promote physical activity and combat non-communicable diseases in similar settings.
Identifying Challenges and Solutions for Improving Access to Mental Health Services for Rural Youth: Insights from Adult Community Members
Authors: Graves Janessa M. , Abshire Demetrius A. , Koontz Elissa , Mackelprang Jessica L.
Published: June 2024

In the rural United States, provider shortages, inadequate insurance coverage, high poverty rates, limited transportation, privacy concerns, and stigma make accessing mental healthcare difficult. Innovative, localized strategies are needed to overcome these barriers, but little is known about what strategies may be feasible in, or acceptable to, rural communities. We aimed to identify barriers youth face in accessing mental healthcare in rural Washington State and to generate ideas to improve access. Methods: Semi-structured, key informant interviews were conducted by telephone with adult community members, including parents, teachers, and healthcare providers. Participants answered questions related to barriers to mental healthcare access that confront youth and approaches to improving access. Detailed, de-identified field notes were analyzed using conventional content analysis. Results: Limited resources and stigma were the two primary barriers to accessing mental healthcare that youth encounter in the community. Limited resources included lack of services and transportation, inconsistent funding and mental health programming, and workforce shortages. Stigma associated with seeking mental healthcare was of particular concern for youth with diverse identities who experience additional stigma. Conclusions: Improving access to mental healthcare for rural youth will require building a strong mental health workforce and championing efforts to reduce stigma associated with help-seeking.
Full-Length Transcriptome Analysis of Skeletal Muscle of Jiangquan Black Pig at Different Developmental Stages
Authors: Song Qi , Li Jinbao , Li Shiyin , Cao Hongzhen , Jin Xinlin , Zeng Yongqing , Chen Wei
Published: June 2024

Skeletal muscle grows in response to a combination of genetic and environmental factors, and its growth and development influence the quality of pork. Elucidating the molecular mechanisms regulating the growth and development of skeletal muscle is of great significance to both animal husbandry and farm management. The Jiangquan black pig is an excellent pig breed based on the original Yimeng black pig, importing the genes of the Duroc pig for meat traits, and cultivated through years of scientific selection and breeding. In this study, full-length transcriptome sequencing was performed on three growth stages of Jiangquan black pigs, aiming to study the developmental changes in Jiangquan black pigs at different developmental stages at the molecular level and to screen the key genes affecting the growth of skeletal muscle in Jiangquan black pigs. We performed an enrichment analysis of genes showing differential expression and constructed a protein–protein interaction network with the aim of identifying core genes involved in the development of Jiangquan black pigs. Notably, genes such as TNNI2, TMOD4, PLDIM3, MYOZ1, and MYH1 may be potential regulators of muscle development in Jiangquan black pigs. Our results contribute to the understanding of the molecular mechanisms of skeletal muscle development in this pig breed, which will facilitate molecular breeding efforts and the development of pig breeds to meet the needs of the livestock industry.
Genome-Wide Identification, Characterization, Evolutionary Analysis, and Expression Pattern of the GPAT Gene Family in Barley and Functional Analysis of HvGPAT18 under Abiotic Stress
Authors: Yang Chenglan , Ma Jianzhi , Qi Cunying , Ma Yinhua , Xiong Huiyan , Duan Ruijun
Published: June 2024

Glycerol-3-phosphoacyltransferase (GPAT) is an important rate-limiting enzyme in the biosynthesis of triacylglycerol (TAG), which is of great significance for plant growth, development, and response to abiotic stress. Although the characteristics of GPAT have been studied in many model plants, little is known about its expression profile and function in barley, especially under abiotic stress. In this study, 22 GPAT genes were identified in the barley genome and divided into three groups (I, II, III), with the latter Group III subdivided further into three subgroups based on the phylogenetic analysis. The analyses of conserved motifs, gene structures, and the three-dimensional structure of HvGPAT proteins also support this classification. Through evolutionary analysis, we determined that HvGPATs in Group I were the earliest to diverge during 268.65 MYA, and the differentiation of other HvGPATs emerged during 86.83–169.84 MYA. The tissue expression profile showed that 22 HvGPAT genes were almost not expressed in INF1 (inflorescence 1). Many functional elements related to stress responses and hormones in cis-element analysis, as well as qRT-PCR results, confirm that these HvGPAT genes were involved in abiotic stress responses. The expression level of HvGPAT18 was significantly increased under abiotic stress and its subcellular localization indicated its function in the endoplasmic reticulum. Various physiological traits under abiotic stress were evaluated using transgenic Arabidopsis to gain further insight into the role of HvGPAT18, and it was found that transgenic seedlings have stronger resistance under abiotic stress than to the wild-type (WT) plants. Overall, our results provide new insights into the evolution and function of the barley GPAT gene family and enable us to explore the molecular mechanism of functional diversity behind the evolutionary history of these genes.
Translational Experimental Basis of Indirect Adenosine Receptor Agonist Stimulation for Bone Regeneration: A Review
Authors: Ehlen Quinn T. , Mirsky Nicholas A. , Slavin Blaire V. , Parra Marcelo , Nayak Vasudev Vivekanand , Cronstein Bruce , Witek Lukasz , Coelho Paulo G.
Published: June 2024

Bone regeneration remains a significant clinical challenge, often necessitating surgical approaches when healing bone defects and fracture nonunions. Within this context, the modulation of adenosine signaling pathways has emerged as a promising therapeutic option, encouraging osteoblast activation and tempering osteoclast differentiation. A literature review of the PubMed database with relevant keywords was conducted. The search criteria involved in vitro or in vivo models, with clear methodological descriptions. Only studies that included the use of indirect adenosine agonists, looking at the effects of bone regeneration, were considered relevant according to the eligibility criteria. A total of 29 articles were identified which met the inclusion and exclusion criteria, and they were reviewed to highlight the preclinical translation of adenosine agonists. While preclinical studies demonstrate the therapeutic potential of adenosine signaling in bone regeneration, its clinical application remains unrealized, underscoring the need for further clinical trials. To date, only large, preclinical animal models using indirect adenosine agonists have been successful in stimulating bone regeneration. The adenosine receptors (A1, A2A, A2B, and A3) stimulate various pathways, inducing different cellular responses. Specifically, indirect adenosine agonists act to increase the extracellular concentration of adenosine, subsequently agonizing the respective adenosine receptors. The agonism of each receptor is dependent on its expression on the cell surface, the extracellular concentration of adenosine, and its affinity for adenosine. This comprehensive review analyzed the multitude of indirect agonists currently being studied preclinically for bone regeneration, discussing the mechanisms of each agonist, their cellular responses in vitro, and their effects on bone formation in vivo.
Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection
Authors: Tai Li-Te , Yeh Cheng-Yun , Chang Yu-Jen , Liu Ju-Fang , Hsu Kai-Cheng , Cheng Ju-Chien , Lu Chih-Hao
Published: June 2024

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein–ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC50 values of 8.8 μM, 6.7 μM, and 7.6 μM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC50 = 5.9 μM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC50 of 9.3 μM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection.
Particulate Matter-Induced Neurotoxicity: Unveiling the Role of NOX4-Mediated ROS Production and Mitochondrial Dysfunction in Neuronal Apoptosis
Authors: Kim Ji-Hee , Hwang Kyu-Hee , Kim Seong-Heon , Kim Hi-Ju , Kim Jung-Min , Lee Mi-Young , Cha Seung-Kuy , Lee Jinhee
Published: June 2024

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.
The Development of Robust Antibodies to Sarcospan, a Dystrophin- and Integrin-Associated Protein, for Basic and Translational Research
Authors: Mokhonova Ekaterina I. , Malik Ravinder , Mamsa Hafsa , Walker Jackson , Gibbs Elizabeth M. , Crosbie Rachelle H.
Published: June 2024

Sarcospan (SSPN) is a 25-kDa transmembrane protein that is broadly expressed at the cell surface of many tissues, including, but not limited to, the myofibers from skeletal and smooth muscles, cardiomyocytes, adipocytes, kidney epithelial cells, and neurons. SSPN is a core component of the dystrophin–glycoprotein complex (DGC) that links the intracellular actin cytoskeleton with the extracellular matrix. It is also associated with integrin α7β1, the predominant integrin expressed in skeletal muscle. As a tetraspanin-like protein with four transmembrane spanning domains, SSPN functions as a scaffold to facilitate protein–protein interactions at the cell membrane. Duchenne muscular dystrophy, Becker muscular dystrophy, and X-linked dilated cardiomyopathy are caused by the loss of dystrophin at the muscle cell surface and a concomitant loss of the entire DGC, including SSPN. SSPN overexpression ameliorates Duchenne muscular dystrophy in the mdx murine model, which supports SSPN being a viable therapeutic target. Other rescue studies support SSPN as a biomarker for the proper assembly and membrane expression of the DGC. Highly specific and robust antibodies to SSPN are needed for basic research on the molecular mechanisms of SSPN rescue, pre-clinical studies, and biomarker evaluations in human samples. The development of SSPN antibodies is challenged by the presence of its four transmembrane domains and limited antigenic epitopes. To address the significant barrier presented by limited commercially available antibodies, we aimed to generate a panel of robust SSPN-specific antibodies that can serve as a resource for the research community. We created antibodies to three SSPN protein epitopes, including the intracellular N- and C-termini as well as the large extracellular loop (LEL) between transmembrane domains 3 and 4. We developed a panel of rabbit antibodies (poly- and monoclonal) against an N-terminal peptide fragment of SSPN. We used several assays to show that the rabbit antibodies recognize mouse SSPN with a high functional affinity and specificity. We developed mouse monoclonal antibodies against the C-terminal peptide and the large extracellular loop of human SSPN. These antibodies are superior to commercially available antibodies and outperform them in various applications, including immunoblotting, indirect immunofluorescence analysis, immunoprecipitation, and an ELISA. These newly developed antibodies will significantly improve the quality and ease of SSPN detection for basic and translational research.
hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice
Authors: Chen Wei , Kim Sharon , Lee Alicia , Kim Yun-Jeong , Chang Chungyu , Ton-That Hung , Kim Reuben , Kim Sangjae , Park No-Hee
Published: June 2024

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer’s disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.
Knockdown of Esr1 from DRD1-Rich Brain Regions Affects Adipose Tissue Metabolism: Potential Crosstalk between Nucleus Accumbens and Adipose Tissue
Authors: Shay Dusti , Welly Rebecca , Mao Jiude , Kinkade Jessica , Brown Joshua K. , Rosenfeld Cheryl S. , Vieira-Potter Victoria J.
Published: June 2024

Declining estrogen (E2) leads to physical inactivity and adipose tissue (AT) dysfunction. Mechanisms are not fully understood, but E2’s effects on dopamine (DA) activity in the nucleus accumbens (NAc) brain region may mediate changes in mood and voluntary physical activity (PA). Our prior work revealed that loss of E2 robustly affected NAc DA-related gene expression, and the pattern correlated with sedentary behavior and visceral fat. The current study used a new transgenic mouse model (D1ERKO) to determine whether the abolishment of E2 receptor alpha (ERα) signaling within DA-rich brain regions affects PA and AT metabolism. Adult male and female wild-type (WT) and D1ERKO (KD) mice were assessed for body composition, energy intake (EE), spontaneous PA (SPA), and energy expenditure (EE); underwent glucose tolerance testing; and were assessed for blood biochemistry. Perigonadal white AT (PGAT), brown AT (BAT), and NAc brain regions were assessed for genes and proteins associated with DA, E2 signaling, and metabolism; AT sections were also assessed for uncoupling protein (UCP1). KD mice had greater lean mass and EE (genotype effects) and a visible change in BAT phenotype characterized by increased UCP1 staining and lipid depletion, an effect seen only among females. Female KD had higher NAc Oprm1 transcript levels and greater PGAT UCP1. This group tended to have improved glucose tolerance (p = 0.07). NAc suppression of Esr1 does not appear to affect PA, yet it may directly affect metabolism. This work may lead to novel targets to improve metabolic dysfunction following E2 loss, possibly by targeting the NAc.
AMELX Mutations and Genotype–Phenotype Correlation in X-Linked Amelogenesis Imperfecta
Authors: Wang Shih-Kai , Zhang Hong , Lin Hua-Chieh , Wang Yin-Lin , Lin Shu-Chun , Seymen Figen , Koruyucu Mine , Simmer James P. , Hu Jan C.-C.
Published: June 2024

AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop’s classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a “snow-capped” appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype–phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3′ truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by “toxic” cellular effects of the mutant proteins.
First Trimester Placental Biomarkers for Pregnancy Outcomes
Authors: Cristodoro Martina , Messa Martina , Tossetta Giovanni , Marzioni Daniela , Dell’Avanzo Marinella , Inversetti Annalisa , Di Simone Nicoletta
Published: June 2024

The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.
Orthologs of NOX5 and EC-SOD/SOD3: dNox and dSod3 Impact Egg Hardening Process and Egg Laying in Reproductive Function of Drosophila melanogaster
Authors: Steinmetz Eva Louise , Scherer Annika , Calvet Célestine , Müller Uli
Published: June 2024

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the ineffectiveness of the antioxidative defense mechanisms. Primary sources of ROS are respiratory electron transfer and the activity of NADPH oxidases (NOX) while superoxide dismutases (SOD) are the main key regulators that control the levels of ROS and reactive nitrogen species intra- and extracellularly. Because of their central role SODs are the subject of research on human ovarian dysfunction but sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study we clarify the localization of the ROS-producing enzyme dNox within the ovaries of Drosophila melanogaster and by a tissue-specific knockdown we show that dNox-derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg-laying behavior but not the chorion hardening process.
The Multifaceted Actions of PVP–Curcumin for Treating Infections
Authors: Metzger Magdalena , Manhartseder Stefan , Krausgruber Leonie , Scholze Lea , Fuchs David , Wagner Carina , Stainer Michaela , Grillari Johannes , Kubin Andreas , Wightman Lionel , Dungel Peter
Published: June 2024

Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP–curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP–curcumin concentrations (1–200 µg/mL) and 475 nm blue light (7.5–45 J/cm2). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP–curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP–curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP–curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.
Biomineral-Based Composite Materials in Regenerative Medicine
Authors: Kim Sung Ho , Ki Mi-Ran , Han Youngji , Pack Seung Pil
Published: June 2024

Regenerative medicine aims to address substantial defects by amplifying the body’s natural regenerative abilities and preserving the health of tissues and organs. To achieve these goals, materials that can provide the spatial and biological support for cell proliferation and differentiation, as well as the micro-environment essential for the intended tissue, are needed. Scaffolds such as polymers and metallic materials provide three-dimensional structures for cells to attach to and grow in defects. These materials have limitations in terms of mechanical properties or biocompatibility. In contrast, biominerals are formed by living organisms through biomineralization, which also includes minerals created by replicating this process. Incorporating biominerals into conventional materials allows for enhanced strength, durability, and biocompatibility. Specifically, biominerals can improve the bond between the implant and tissue by mimicking the micro-environment. This enhances cell differentiation and tissue regeneration. Furthermore, biomineral composites have wound healing and antimicrobial properties, which can aid in wound repair. Additionally, biominerals can be engineered as drug carriers, which can efficiently deliver drugs to their intended targets, minimizing side effects and increasing therapeutic efficacy. This article examines the role of biominerals and their composite materials in regenerative medicine applications and discusses their properties, synthesis methods, and potential uses.
Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis
Authors: Wasserer Sophia , Jargosch Manja , Mayer Kristine E. , Eigemann Jessica , Raunegger Theresa , Aydin Görkem , Eyerich Stefanie , Biedermann Tilo , Eyerich Kilian , Lauffer Felix
Published: June 2024

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders.
The Balance between Protealysin and Its Substrate, the Outer Membrane Protein OmpX, Regulates Serratia proteamaculans Invasion
Authors: Tsaplina Olga
Published: June 2024

Serratia are opportunistic bacteria, causing infections in plants, insects, animals and humans under certain conditions. The development of bacterial infection in the human body involves several stages of host–pathogen interaction, including entry into non-phagocytic cells to evade host immune cells. The facultative pathogen Serratia proteamaculans is capable of penetrating eukaryotic cells. These bacteria synthesize an actin-specific metalloprotease named protealysin. After transformation with a plasmid carrying the protealysin gene, noninvasive E. coli penetrate eukaryotic cells. This suggests that protealysin may play a key role in S. proteamaculans invasion. This review addresses the mechanisms underlying protealysin’s involvement in bacterial invasion, highlighting the main findings as follows. Protealysin can be delivered into the eukaryotic cell by the type VI secretion system and/or by bacterial outer membrane vesicles. By cleaving actin in the host cell, protealysin can mediate the reversible actin rearrangements required for bacterial invasion. However, inactivation of the protealysin gene leads to an increase, rather than decrease, in the intensity of S. proteamaculans invasion. This indicates the presence of virulence factors among bacterial protealysin substrates. Indeed, protealysin cleaves the virulence factors, including the bacterial surface protein OmpX. OmpX increases the expression of the EGFR and β1 integrin, which are involved in S. proteamaculans invasion. It has been shown that an increase in the invasion of genetically modified S. proteamaculans may be the result of the accumulation of full-length OmpX on the bacterial surface, which is not cleaved by protealysin. Thus, the intensity of the S. proteamaculans invasion is determined by the balance between the active protealysin and its substrate OmpX.
Antibodies Targeting Human or Mouse VSIG4 Repolarize Tumor-Associated Macrophages Providing the Potential of Potent and Specific Clinical Anti-Tumor Response Induced across Multiple Cancer Types
Authors: Sazinsky Stephen , Zafari Mohammad , Klebanov Boris , Ritter Jessica , Nguyen Phuong A. , Phennicie Ryan T. , Wahle Joe , Kauffman Kevin J. , Razlog Maja , Manfra Denise , Feldman Igor , Novobrantseva Tatiana
Published: June 2024

V-set immunoglobulin domain-containing 4 (VSIG4) is a B7 family protein with known roles as a C3 fragment complement receptor involved in pathogen clearance and a negative regulator of T cell activation by an undetermined mechanism. VSIG4 expression is specific for tumor-associated and select tissue-resident macrophages. Increased expression of VSIG4 has been associated with worse survival in multiple cancer indications. Based upon computational analysis of transcript data across thousands of tumor and normal tissue samples, we hypothesized that VSIG4 has an important role in promoting M2-like immune suppressive macrophages and that targeting VSIG4 could relieve VSIG4-mediated macrophage suppression by repolarizing tumor-associated macrophages (TAMs) to an inflammatory phenotype. We have also observed a cancer-specific pattern of VSIG4 isoform distribution, implying a change in the functional regulation in cancer. Through a series of in vitro, in vivo, and ex vivo assays we demonstrate that anti-VSIG4 antibodies repolarize M2 macrophages and induce an immune response culminating in T cell activation. Anti-VSIG4 antibodies induce pro-inflammatory cytokines in M-CSF plus IL-10-driven human monocyte-derived M2c macrophages. Across patient-derived tumor samples from multiple tumor types, anti-VSIG4 treatment resulted in the upregulation of cytokines associated with TAM repolarization and T cell activation and chemokines involved in immune cell recruitment. VSIG4 blockade is also efficacious in a syngeneic mouse model as monotherapy as it enhances efficacy in combination with anti-PD-1, and the effect is dependent on the systemic availability of CD8+ T cells. Thus, VSIG4 represents a promising new target capable of triggering an anti-cancer response via multiple key immune mechanisms.
An Overview of Epigenetic Changes in the Parkinson’s Disease Brain
Authors: Klokkaris Anthony , Migdalska-Richards Anna
Published: June 2024

Parkinson’s disease is a progressive neurodegenerative disorder, predominantly of the motor system. Although some genetic components and cellular mechanisms of Parkinson’s have been identified, much is still unknown. In recent years, emerging evidence has indicated that non-DNA-sequence variation (in particular epigenetic mechanisms) is likely to play a crucial role in the development and progression of the disease. Here, we present an up-to-date overview of epigenetic processes including DNA methylation, DNA hydroxymethylation, histone modifications and non-coding RNAs implicated in the brain of those with Parkinson’s disease. We will also discuss the limitations of current epigenetic research in Parkinson’s disease, the advantages of simultaneously studying genetics and epigenetics, and putative novel epigenetic therapies.
Study on the Effects of Angiotensin Receptor/Neprilysin Inhibitors on Renal Haemodynamics in Healthy Dogs
Authors: Ishizaka Mio , Yamamori Yurika , Hsu Huai-Hsun , Miyagawa Yuichi , Takemura Naoyuki , Ogawa-Yasumura Mizuki
Published: June 2024

An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.
Influence of Ethanol Grade on Captures of Ambrosia Beetles in Tree Fruit Orchards, Ornamental Nurseries, and Lumber Yards
Authors: Dzurenko Marek , Ranger Christopher M. , Pavlík Martin , Reding Michael E.
Published: June 2024

Ambrosia beetles, particularly invasive species within the tribe Xyleborini, such as Xylosandrus germanus (Blandford, 1894), pose significant threats to various ecosystems and managed habitats worldwide. Monitoring these invaders is vital for effective pest management, typically accomplished through ethanol-baited traps. We compared trap efficacy using denatured ethanol versus absolute ethanol in orchards, tree nurseries, and lumber yards in northeastern Ohio, USA, finding that absolute ethanol traps captured significantly more X. germanus. Analysis revealed acetone, ethanol, and methyl isobutyl ketone in the denatured ethanol, likely impacting trap efficacy. Our study underscores the importance of using pure denatured ethanol without acetone for effective monitoring, especially for X. germanus. Exotic xyleborines dominated trap captures across various habitats, emphasizing the need for tailored pest management strategies. Further research is warranted to explore the chemical ecology of ambrosia beetles and the influence of ethanol impurities on trap effectiveness.
Oxalic Acid Treatment: Short-Term Effects on Enzyme Activities, Vitellogenin Content, and Residual Oxalic Acid Content in House Bees, Apis mellifera L.
Authors: Sagona Simona , Tafi Elena , Coppola Francesca , Nanetti Antonio , Boni Chiara Benedetta , Orlando Caterina , Palego Lionella , Betti Laura , Giannaccini Gino , Felicioli Antonio
Published: June 2024

Honeybees (Apis mellifera L.) have to face many challenges, including Varroa destructor infestation, associated with viral transmission. Oxalic acid is one of the most common treatments against Varroa. Little is known about the physiological effects of oxalic acid, especially those on honeybees’ immune systems. In this study, the short-term effects (0–96 h) of oxalic acid treatment on the immune system components (i.e., glucose oxidase, phenoloxidase, glutathione S-transferase, catalase activities, and vitellogenin contents) of house bees were preliminarily investigated. Oxalic acid contents of bee bodies and haemolymphs were also measured. The results confirm that oxalic acid is constitutively present in bee haemolymphs and its concentration is not affected by treatment. At 6 h after the treatment, a maximum peak of oxalic acid content was detected on bees’ bodies, which gradually decreased after that until physiological levels were reached at 48 h. In the immune system, the oxalic acid treatment determined a peak in glucose oxidase activity at 48 h, indicating a potential defence response and an increase in vitellogenin content at 24 h. No significant changes were recorded in phenoloxidase, glutathione S-transferase, and catalase activities. These results suggest a time-dependent response to oxalic acid, with potential immune system activation in treated bees.
Feeding Performance of Argentine Stem Weevil Is Reduced by Peramine from Perennial Ryegrass Infected with Endophyte Fungus
Authors: Chacón-Fuentes Manuel , Martínez-Cisterna Daniel , Vera Waleska , Ortega-Klose Fernando , Reyes Claudio , Matamala Ignacio , Quiroz Andrés , Bardehle Leonardo
Published: June 2024

One of the primary supports for extensive agriculture is pasture, which can suffer severe damage from insects including the Argentine stem weevil, Listronotus bonariensis. The main control method has been the infection of ryegrass with an endophyte fungus, forming a symbiotic association that produces alkaloids. In this study, we evaluated the impact of endophyte and peramine production on the weight of L. bonariensis across seven unnamed lines (LE161-LE167), and two Lolium perenne cultivars: Jumbo and Alto AR1. L. bonariensis adults fed on leaves from LE164, LE166, and ALTO AR1 showed weight losses of 13.3%, 17.1% and 18.2%, respectively. Similarly, the corresponding alkaloidal extract from LE164, LE166, and ALTO AR1 exhibited an antifeedant effect on L. bonariensis adults in laboratory assays, as observed through weight loss or low weight gain (−12.5%, 8.8% and 4.9%, respectively). Furthermore, one alkaloid, peramine, also elicited an antifeedant effect when incorporated into an artificial diet. Liquid chromatographic analysis of the alkaloid extract revealed that peramine was present in LE164, LE166 and ALTO AR1 in amounts ranging from 46.5–184.2 ng/g. Peramine was not detected in Jumbo and the remaining experimental lines. These data suggest that L. bonariensis were susceptible to peramine produced from endophyte infection in experimental lines LE164 and LE166, as well as ALTO AR1, affecting their feeding behavior.