bluuebunny/crossref_metadata_2025 huggingface dataset:
A Focus on the Proximal Tubule Dysfunction in Dent Disease Type 1
Authors: de Combiens Elise , Sakhi Imene Bouchra , Lourdel Stéphane
Published: September 2024

Dent disease type 1 is a rare X-linked recessive inherited renal disorder affecting mainly young males, generally leading to end-stage renal failure and for which there is no cure. It is caused by inactivating mutations in the gene encoding ClC-5, a 2Cl−/H+ exchanger found on endosomes in the renal proximal tubule. This transporter participates in reabsorbing all filtered plasma proteins, which justifies why proteinuria is commonly observed when ClC-5 is defective. In the context of Dent disease type 1, a proximal tubule dedifferentiation was shown to be accompanied by a dysfunctional cell metabolism. However, the exact mechanisms linking such alterations to chronic kidney disease are still unclear. In this review, we gather knowledge from several Dent disease type 1 models to summarize the current hypotheses generated to understand the progression of this disorder. We also highlight some urinary biomarkers for Dent disease type 1 suggested in different studies.
Physiological and Transcriptome Analyses Reveal the Effects of Fertilization on the Yield of Winter Wheat and on the Photosynthetic Performance of Leaves during the Flowering Period
Authors: Wang Lihong , Shi Jia , Zhang Hongzhi , Chen Xunji , Li Jianfeng , Wang Zhong , Li Xiaorong , Gao Xin , Wang Chunsheng , Xia Jianqiang , Zhao Zhun , Zhang Yueqiang , Fan Zheru , Zhao Qi
Published: September 2024

Fertilization significantly affects the growth and development of wheat. However, the precise mechanisms underlying gene regulation during flowering in response to fertilization deficiency remain elusive. In this study, fertilization (F) and non-fertilization (CK) ) treatments were set up to reveal examine the effect of fertilization on the photosynthetic capacity of winter wheat during the flowering period through physiological, biochemical, and transcriptome analyses. Upon analyzing analysing their yield, leaf photosynthetic system exchange parameters during flowering, antioxidant enzyme activity, and endogenous hormone parameters, we found that the F treatment resulted in higher net photosynthetic rates during flowering periods than the CK treatment. The superoxide dismutase (SOD) (83.92%), peroxidase (POD) (150.75%), and catalase (CAT) (22.74%) activities of leaves in treated with F during the flowering period were notably elevated compared to those of CK-treated leaves. Abscisic acid (ABA) (1.86%) and gibberellin acid (GA3) (33.69%) levels were reduced, whereas Auxin auxin (IAA) (98.27%) content was increasedwas increased under F treatment compared to those the results under the CK treatment. The chlorophyll a (32.53%), chlorophyll b (56%), total chlorophyll (37.96%), and carotenoid contents (29.80%) under F treatment were also increased compared to CK., exceeded exceeding those obtained under the CK treatment. Furthermore, transcriptional differences between the F and CK conditions were analyzed, and key genes were screened and validated by using q-PCR. Transcriptome analysis identified 2281 differentially expressed genes (DEGs), with enriched pathways related to photosynthesis and light harvesting. DEGs were subjected to cluster simulation, which revealed that 53 DEGS, both up- and down-regulated, responded to the F treatment. qRT-PCR-based validation confirmed the differential expression of genes associated with carbohydrate transport and metabolism, lipid transport, and signal transduction. This study revealed distinctive transcriptional patterns and crucial gene regulation networks in wheat during flowering under fertilization, providing transcriptomic guidance for the precise regulation of wheat breeding.
Genetic Diversity and Divergence between Southern Japonica and Northern Japonica Rice Varieties in China
Authors: Yan Zhiqiang , Deng Ruyue , Tang Huihui , Zhu Susong
Published: September 2024

Given the notable ecological and breeding disparities between southern and northern rice regions, delving into the genetic diversity and divergence between southern and northern japonica rice contributes to enhancing the genetic pool for japonica rice breeding. In this study, we analyzed 90 southern and 51 northern japonica rice varieties, focusing on nucleotide diversity (Pi), agronomic trait variations, population structure, genetic divergence, and a neutral test. For genetic diversity, the results demonstrated higher Pi in northern japonica rice varieties (NJRVs) on Chr2, Chr5, Chr6, Chr8, and Chr10, whereas in southern japonica rice varieties (SJRVs) on Chr7 and Chr9. In addition, SJRVs exhibited higher grain width and thickness, whereas NJRVs featured a higher grain aspect ratio, filled grain number, and grain number per panicle. Regarding genetic divergence, geographic differentiation existed between NJRVs and SJRVs, with Chr5 exhibiting numerous higher genetic differentiation windows, including cloned grain shape-controlling genes RGA1 and SFD5, stemming from intensified selection pressure on SJRVs. In summary, SJRVs and NJRVs exhibited diversity differences and genetic differentiation. Hence, it was suggested to conduct genetic introgression between NJRVs and SJRVs to broaden the genetic basis of the local japonica rice germplasm. By exploiting their heterotic advantage, new japonica rice cultivars with superior comprehensive traits could be developed.
Review on Constitutive Model for Simulation of Weak Rock Mass
Authors: Azadi Ava , Momayez Moe
Published: September 2024

Understanding the behavior of weak rock masses is important for predicting the stability of structures under different loading conditions. Traditional models such as the generalized Hoek–Brown and Coulomb weak plane are widely used; however, they often fail to capture the nonlinear and irreversible behavior of weak rock masses. This study offers a comprehensive overview of a critical analysis of constitutive models’ strengths and limitations for simulating weak rock masses. By comparing traditional and advanced novel approaches such as the strength degradation of rock (SDR) masses and continuous damage mechanics (CDM), this investigation shows that the new advanced methods significantly enhance the quality and accuracy of simulations. Moreover, SDR models address the limitations of classical plasticity models by incorporating nonlinear stress paths and irreversible stress changes, while CDM offers detailed insights into microstructural defect progression. These advancements allow for more accurate and practical predictions of long-term stability in geomechanical engineering tailored to specific requirements of each project.
Parent–Child Mismatch in Educational Expectations and Depressive Symptoms among Chinese Adolescents
Authors: Zhang Yueyun , Jiang Meng
Published: September 2024

Background: The roles of both parents’ and children’s educational expectations in shaping adolescent depressive symptoms have increasingly been discussed, yet in a separate manner. To date, few studies have associated parent–child mismatch in educational expectations with depressive symptoms, and less is known about the variation in the association across gender (male vs. female), educational level (primary vs. secondary), and region status (urban vs. rural) in the Chinese educational setting. Methods: Respondents were from a nationally representative sample of adolescent students in China (sample size: 1844; age range: 10–15 years). Parent–child mismatch in educational expectations included three categories: (1) “match”, (2) “mismatch—parent higher”, and (3) “mismatch—parent lower”. Regression analysis with inverse propensity-score weighting was employed to estimate the effect of parent–child mismatch as to educational expectations on depressive symptoms, and stratified analysis was used to examine the variation of the effect by gender, educational level, and region. Results: Compared with the “match” group, the “mismatch—parent higher” group had significantly higher levels of depressive symptoms. Furthermore, the pattern remained consistent between boys and girls, but differed significantly by adolescents’ educational level and region status. Specifically, the pattern was more pronounced in the primary school and urban subsamples. Conclusions: Findings in this study indicated that educators and policymakers can develop tailored strategies to alleviate depressive symptoms among the “mismatch—parent higher” group, and especially for those children from primary schools and urban areas.
Comparison of Self-Care Practices and BMI between Celiac and Non-Celiac Adolescent Populations
Authors: Monserrat-Hernández Montserrat , Checa-Olmos Juan Carlos , Garrido Ángeles Arjona , Galera-Martínez Rafael
Published: September 2024

Celiac disease (CD) is a chronic gastrointestinal disorder that is most frequently found in Western countries, and the only treatment available today is a lifelong gluten-free diet (GFD). The main aim of the present study is to compare the self-care practices and body mass index (BMI) of adolescents with CD and without CD in different dimensions (physical, psychological, social, and management). The non-probabilistic sample included 236 participants (118 with CD) aged between 12 and 16 years old, who were part of the project “Role of the family in the perception of youth self-care”. The data were obtained through the self-administration of the Practice and Management of Youth Self-care questionnaire, while the celiac population also completed the Adherence to a Gluten-Free Diet (GFD) questionnaire. The celiac population analyzed showed significant correlations between the Physical Practices and Management with adherence to a GFD, and between a GFD and Psychological Practices. Differences were observed between the celiac and the non-celiac populations in the dimensions of Physical Practices, Social Practices, and Management. With respect to BMI, age and CD showed a significant influence of a GFD on BMI (p < 0.001). In conclusion, the application of multi-dimensional questionnaires and their relationship with the adherence to a GFD provide valuable information to propose interventions directed to this population.
UAV, GNSS, Total Station, and Data Management Applied to an Ancient Clay Structure as a Historic Building Information Modeling Proposal: A Case Study of Huaca Arco Iris (Trujillo, Peru)
Authors: Espinoza Brugman Carlos Antonio , Neri Caipo Frank Kevin , Almeida Del Savio Alexandre
Published: September 2024

In light of current risks and environmental impacts, HBIM (historic building information modeling) offers a highly efficient and interactive method for managing historical data and representing the current states of ancient clay structures. In this study, traditional geodetic techniques were employed to digitally locate a structure without compromising its topographic information to create an accurate model. Tools such as total stations, GNSS receivers, and UAVs were utilized to generate detailed topography of the study site and its surroundings. An ontology-based data management structure was also developed to store historical data and site intervention projects, adhering to the ISO 12006-2 standard. This was achieved through automated scripts in Dynamo softwarev.2.18.1. A comparison between the point cloud (279 images) and total station data (600 points) revealed a georeferencing accuracy difference of +/−0.003 m. Consequently, the developed methods can effectively represent similar structures digitally. The proposed ontological structure facilitates automated storage of internal and external information.
A Transcriptomic Analysis of Laryngeal Dysplasia
Authors: Maffini Fausto , Lepanto Daniela , Chu Francesco , Tagliabue Marta , Vacirca Davide , De Berardinis Rita , Gandini Sara , Vignati Silvano , Ranghiero Alberto , Taormina Sergio , Rappa Alessandra , Cossu Rocca Maria , Alterio Daniela , Chiocca Susanna , Barberis Massimo , Preda Lorenzo , Pagni Fabio , Fusco Nicola , Ansarin Mohssen
Published: September 2024

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery. These transcriptional alterations were observed using the RNA-based next-generation sequencing (NGS) panel Oncomine Immune Response Research Assay (OIRRA) to measure the expression of genes associated with lymphocyte regulation, cytokine signaling, lymphocyte markers, and checkpoint pathways. During the analysis, it became apparent that certain alterations divide dysplasia into two categories: progressive or not. In the future, these biological alterations are the first step to provide new treatment modalities with different classes of drugs currently in use in a systemic or local approach, including classical chemotherapy drugs such as cisplatin and fluorouracile, older drugs like fenretinide, and new checkpoint inhibitor drugs such as nivolumab and pembrolizumab, as well as newer options like T cell therapy (CAR-T). Following these observed alterations, it is possible to differentiate which dysplasias progress or not or relapse quickly. This information could, in the future, be the basis for determining a close follow-up, minimizing surgical interventions, planning a correct and personalized treatment protocol for each patient and, after specific clinical trials, tailoring new drug treatments.
In Vitro Spectroscopic Investigation of Losartan and Glipizide Competitive Binding to Glycated Albumin: A Comparative Study
Authors: Szkudlarek Agnieszka
Published: September 2024

Understanding the interaction between pharmaceuticals and serum proteins is crucial for optimizing therapeutic strategies, especially in patients with coexisting chronic diseases. The primary goal of this study was to assess the potential changes in binding affinity and competition between glipizide (GLP, a second-generation sulfonylurea hypoglycemic drug) and losartan (LOS, a medication commonly prescribed for hypertension, particularly for patients with concurrent diabetes) with non-glycated (HSA) and glycated (gHSAGLC, gHSAFRC) human serum albumin using multiple spectroscopic techniques (fluorescence, UV-visible absorption, and circular dichroism spectroscopy). The results indicated that FRC is a more effective glycation agent for HSA than GLC, significantly altering the albumin structure and affecting the microenvironment around critical amino acid residues, Trp-214 and Tyr. These modifications reduce the binding affinity of LOS and GLP to gHSAGLC and gHSAFRC, compared to HSA, resulting in less stable drug–protein complexes. The study revealed that LOS and GLP interact nonspecifically with the hydrophobic regions of the albumin surface in both binary (ligand–albumin) and ternary systems (ligand–albumin–ligandconst) and specifically saturate the binding sites within the protein molecule. Furthermore, the presence of an additional drug (GLP in the LOS–albumin complex or LOS in the GLP–albumin complex) complicates the interactions, likely leading to competitive binding or displacement of the initially bound drug in both non-glycated and glycated albumins. Analysis of the CD spectra suggests mutual interactions between GLP and LOS, underscoring the importance of closely monitoring patients co-administered these drugs, to ensure optimal therapeutic efficacy and safety.
Mitochondria and Acute Leukemia: A Clinician’s Perspective
Authors: Iyer Prasad , Jasdanwala Shaista Shabbir , Bhatia Karanpreet , Bhatt Shruti
Published: September 2024

Acute leukemia is a group of aggressive hematological malignancies, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the most common types. The biology of acute leukemia involves complex genetic and epigenetic alterations that lead to uncontrolled cell proliferation and resistance to apoptosis. Mitochondrial dysfunction is a feature of acute leukemia that results in altered energy production, unregulated cell death pathways, and increased cancer cell survival. Apoptosis, particularly via the mitochondrial pathway, is crucial for cellular homeostasis and cancer prevention. In acute leukemia, disruption of apoptosis is pivotal in disease development and progression, with elevated levels of anti-apoptotic proteins conferring a survival advantage to leukemia cells and promoting resistance to conventional therapies. Targeting mitochondrial apoptosis using BH3 mimetics and anti-apoptotic protein inhibitors is a viable therapeutic strategy. Alterations in the mitochondrial membrane potential, metabolism, and dynamics also contribute to the pathogenesis of acute leukemia. Continued research is vital for developing novel therapies and enhancing survival outcomes in patients with acute leukemia while minimizing the long-term adverse effects of treatment. In this narrative review, we provide a birds-eye view of the available scientific literature on the importance of mitochondria in acute leukemia, and discuss the role of BH3 mimetics in targeting the mitochondrial internal apoptotic machinery.
Genetic and Epigenetic Interactions Involved in Senescence of Stem Cells
Authors: Iordache Florin , Petcu Adriana Cornelia Ionescu , Alexandru Diana Mihaela
Published: September 2024

Cellular senescence is a permanent condition of cell cycle arrest caused by a progressive shortening of telomeres defined as replicative senescence. Stem cells may also undergo an accelerated senescence response known as premature senescence, distinct from telomere shortening, as a response to different stress agents. Various treatment protocols have been developed based on epigenetic changes in cells throughout senescence, using different drugs and antioxidants, senolytic vaccines, or the reprogramming of somatic senescent cells using Yamanaka factors. Even with all the recent advancements, it is still unknown how different epigenetic modifications interact with genetic profiles and how other factors such as microbiota physiological conditions, psychological states, and diet influence the interaction between genetic and epigenetic pathways. The aim of this review is to highlight the new epigenetic modifications that are involved in stem cell senescence. Here, we review recent senescence-related epigenetic alterations such as DNA methylation, chromatin remodeling, histone modification, RNA modification, and non-coding RNA regulation outlining new possible targets for the therapy of aging-related diseases. The advantages and disadvantages of the animal models used in the study of cellular senescence are also briefly presented.
Interaction of Micro- and Nanoplastics with Enzymes: The Case of Carbonic Anhydrase
Authors: Polo Gregorio , Lionetto Francesca , Giordano Maria Elena , Lionetto Maria Giulia
Published: September 2024

Microplastics (MPs) and nanoplastics (NPs) have emerged as significant environmental pollutants with potential detrimental effects on ecosystems and human health. Several studies indicate their interaction with enzymes; this topic represents a multifaceted research field encompassing several areas of interest from the toxicological and ecotoxicological impact of MPs and NPs on humans and wildlife to the biodegradation of plastics by microbial enzymes. This review aims to provide a critical analysis of the state-of-the-art knowledge of the interaction of MPs and NPs on the enzyme carbonic anhydrase (CA), providing recent insights, analyzing the knowledge gaps in the field, and drawing future perspectives of the research and its application. CA is a widespread and crucial enzyme in various organisms; it is critical for various physiological processes in animals, plants, and bacteria. It catalyzes the reversible hydration of CO2, which is essential for respiration, acid–base balance, pH homeostasis, ion transport, calcification, and photosynthesis. Studies demonstrate that MPs and NPs can inhibit CA activity with mechanisms including adsorption to the enzyme surface and subsequent conformational changes. In vitro and in silico studies highlight the role of electrostatic and hydrophobic interactions in these processes. In vivo studies present mixed results, which are influenced by factors like particle type, size, concentration, and organism type. Moreover, the potentiality of the esterase activity of CA for plastic degradation is discussed. The complexity of the interaction between CA and MPs/NPs underscores the need for further research to fully understand the ecological and health impacts of MPs and NPs on CA activity and expression and glimpses of the potentiality and perspectives in this field.
Thiostrepton as a Potential Therapeutic Agent for Hepatocellular Carcinoma
Authors: Su Guifeng , Yang Qianqing , Zhou Heyang , Huang Ying , Nie Shiyun , Wang Dan , Ma Guangchao , Zhang Shaohua , Kong Lingmei , Zou Chenggang , Li Yan
Published: September 2024

Due to limited drug efficacy and drug resistance, it is urgent to explore effective anti-liver cancer drugs. Repurposing drugs is an efficient strategy, with advantages including reduced costs, shortened development cycles, and assured safety. In this study, we adopted a synergistic approach combining computational and experimental methods and identified the antibacterial drug thiostrepton (TST) as a candidate for an anti-liver cancer drug. Although the anti-tumor capabilities of TST have been reported, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unclear. TST was found here to inhibit the proliferation of HCC cells effectively, arresting the cell cycle and inducing cell apoptosis, as well as suppressing the cell migration. Further, our findings revealed that TST induced mitochondrial impairment, which was demonstrated by destroyed mitochondrial structures, reduced mitochondria, and decreased mitochondrial membrane potential (MMP). TST caused the production of reactive oxygen species (ROS), and the mitochondrial impairment and proliferation inhibition of HCC cells were completely restored by the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we discovered that TST induced mitophagy, and autophagy inhibition effectively promoted the anti-cancer effects of TST on HCC cells. In conclusion, our study suggests TST as a promising candidate for the treatment of liver cancers, and these findings provide theoretical support for the further development and potential application of TST in clinical liver cancer therapy.
The Underlying Molecular Mechanisms of the Placenta Accreta Spectrum: A Narrative Review
Authors: Lizárraga-Verdugo Erik , Beltrán-Ontiveros Saúl Armando , Gutiérrez-Grijalva Erick Paul , Montoya-Moreno Marisol , Gutiérrez-Arzapalo Perla Y. , Avendaño-Félix Mariana , Gutiérrez-Castro Karla Paola , Cuén-Lazcano Daniel E. , González-Quintero Paul , Mora-Palazuelos Carlos Ernesto
Published: September 2024

Placenta accreta spectrum (PAS) disorders are characterized by abnormal trophoblastic invasion into the myometrium, leading to significant maternal health risks. PAS includes placenta accreta (invasion < 50% of the myometrium), increta (invasion > 50%), and percreta (invasion through the entire myometrium). The condition is most associated with previous cesarean deliveries and increases in chance with the number of prior cesarians. The increasing global cesarean rates heighten the importance of early PAS diagnosis and management. This review explores genetic expression and key regulatory processes, such as apoptosis, cell proliferation, invasion, and inflammation, focusing on signaling pathways, genetic expression, biomarkers, and non-coding RNAs involved in trophoblastic invasion. It compiles the recent scientific literature (2014–2024) from the Scopus, PubMed, Google Scholar, and Web of Science databases. Identifying new biomarkers like AFP, sFlt-1, β-hCG, PlGF, and PAPP-A aids in early detection and management. Understanding genetic expression and non-coding RNAs is crucial for unraveling PAS complexities. In addition, aberrant signaling pathways like Notch, PI3K/Akt, STAT3, and TGF-β offer potential therapeutic targets to modulate trophoblastic invasion. This review underscores the need for interdisciplinary care, early diagnosis, and ongoing research into PAS biomarkers and molecular mechanisms to improve prognosis and quality of life for affected women.
Glucose-Dependent Insulinotropic Polypeptide Inhibits AGE-Induced NADPH Oxidase-Derived Oxidative Stress Generation and Foam Cell Formation in Macrophages Partly via AMPK Activation
Authors: Terasaki Michishige , Yashima Hironori , Mori Yusaku , Saito Tomomi , Inoue Naoto , Matsui Takanori , Osaka Naoya , Fujikawa Tomoki , Ohara Makoto , Yamagishi Sho-ichi
Published: September 2024

Glucose-dependent insulinotropic polypeptide (GIP) of the incretin group has been shown to exert pleiotropic actions. There is growing evidence that advanced glycation end products (AGEs), senescent macromolecules formed at an accelerated rate under chronic hyperglycemic conditions, play a role in the pathogenesis of atherosclerotic cardiovascular disease in diabetes. However, whether and how GIP could inhibit the AGE-induced foam cell formation of macrophages, an initial step of atherosclerosis remains to be elucidated. In this study, we address these issues. We found that AGEs increased oxidized low-density-lipoprotein uptake into reactive oxygen species (ROS) generation and Cdk5 and CD36 gene expressions in human U937 macrophages, all of which were significantly blocked by [D-Ala2]GIP(1–42) or an inhibitor of NADPH oxidase activity. An inhibitor of AMP-activated protein kinase (AMPK) attenuated all of the beneficial effects of [D-Ala2]GIP(1–42) on AGE-exposed U937 macrophages, whereas an activator of AMPK mimicked the effects of [D-Ala2]GIP(1–42) on foam cell formation, ROS generation, and Cdk5 and CD36 gene expressions in macrophages. The present study suggests that [D-Ala2]GIP(1–42) could inhibit the AGE-RAGE-induced, NADPH oxidase-derived oxidative stress generation in U937 macrophages via AMPK activation and subsequently suppress macrophage foam cell formation by reducing the Cdk5-CD36 pathway.
Utilizing Molecular Dynamics Simulations, Machine Learning, Cryo-EM, and NMR Spectroscopy to Predict and Validate Protein Dynamics
Authors: Son Ahrum , Kim Woojin , Park Jongham , Lee Wonseok , Lee Yerim , Choi Seongyun , Kim Hyunsoo
Published: September 2024

Protein dynamics play a crucial role in biological function, encompassing motions ranging from atomic vibrations to large-scale conformational changes. Recent advancements in experimental techniques, computational methods, and artificial intelligence have revolutionized our understanding of protein dynamics. Nuclear magnetic resonance spectroscopy provides atomic-resolution insights, while molecular dynamics simulations offer detailed trajectories of protein motions. Computational methods applied to X-ray crystallography and cryo-electron microscopy (cryo-EM) have enabled the exploration of protein dynamics, capturing conformational ensembles that were previously unattainable. The integration of machine learning, exemplified by AlphaFold2, has accelerated structure prediction and dynamics analysis. These approaches have revealed the importance of protein dynamics in allosteric regulation, enzyme catalysis, and intrinsically disordered proteins. The shift towards ensemble representations of protein structures and the application of single-molecule techniques have further enhanced our ability to capture the dynamic nature of proteins. Understanding protein dynamics is essential for elucidating biological mechanisms, designing drugs, and developing novel biocatalysts, marking a significant paradigm shift in structural biology and drug discovery.
LncRNAs Are Key Regulators of Transcription Factor-Mediated Endothelial Stress Responses
Authors: Lam Frederike , Leisegang Matthias S. , Brandes Ralf P.
Published: September 2024

The functional role of long noncoding RNAs in the endothelium is highly diverse. Among their many functions, regulation of transcription factor activity and abundance is one of the most relevant. This review summarizes the recent progress in the research on the lncRNA–transcription factor axes and their implications for the vascular endothelium under physiological and pathological conditions. The focus is on transcription factors critical for the endothelial response to external stressors, such as hypoxia, inflammation, and shear stress, and their lncRNA interactors. These regulatory interactions will be exemplified by a selected number of lncRNAs that have been identified in the endothelium under physiological and pathological conditions that are influencing the activity or protein stability of important transcription factors. Thus, lncRNAs can add a layer of cell type-specific function to transcription factors. Understanding the interaction of lncRNAs with transcription factors will contribute to elucidating cardiovascular disease pathologies and the development of novel therapeutic approaches.
Hypertriglyceridemia Therapy: Past, Present and Future Perspectives
Authors: Canfora Ileana , Pierno Sabata
Published: September 2024

Hypertriglyceridemia therapy is essential for preventing cardiovascular diseases. Fibrates belong to an important class of lipid-lowering drugs useful for the management of dyslipidaemia. By acting on the peroxisome proliferator-activated receptor (PPAR)-α, these drugs lower serum triglyceride levels and raise high-density lipoprotein cholesterol. Fibrate monotherapy is associated with a risk of myopathy and this risk is enhanced when these agents are administered together with statins. However, whereas gemfibrozil can increase plasma concentrations of statins, fenofibrate has less influence on the pharmacokinetics of statins. Pemafibrate is a new PPAR-α-selective drug considered for therapy, and clinical trials are ongoing. Apart from this class of drugs, new therapies have emerged with different mechanisms of action to reduce triglycerides and the risk of cardiovascular diseases.
8-Prenylgenistein Isoflavone in Cheonggukjang Acts as a Novel AMPK Activator Attenuating Hepatic Steatosis by Enhancing the SIRT1-Mediated Pathway
Authors: Arulkumar Radha , Jung Hee Jin , Noh Sang Gyun , Kim Hyun Woo , Chung Hae Young
Published: September 2024

8-Prenylgenistein (8PG), a genistein derivative, is present in fermented soybeans (Glycine max), including cheonggukjang (CGJ), and exhibits osteoprotective, osteogenic, and antiadipogenic properties. However, the hepatoprotective effects of 8PG and its underlying molecular mechanisms remain largely unexplored. Here, we identified the high binding affinity of 8PG with AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), which acts as a potent AMPK activator that counteracts hepatic steatosis. Notably, 8PG exhibited better pharmacokinetics with greater absorption and higher plasma binding than the positive controls for the target proteins. Moreover, 8PG exerted non-carcinogenic activity in rats and significantly increased AMPK phosphorylation. Compound C, an AMPK inhibitor, did not antagonize 8PG-activated AMPK in HepG2 cells. 8PG significantly attenuated palmitate-induced lipid accumulation and enhanced phosphorylated AMPK and its downstream target, acetyl-CoA carboxylase. Further, 8PG activated nuclear SIRT1 at the protein level, which promoted fatty acid oxidation in palmitate-treated HepG2 cells. Overall, 8PG acts as a potent AMPK activator, further attenuating hepatic steatosis via the SIRT1-mediated pathway and providing new avenues for dietary interventions to treat metabolic dysfunction-associated steatotic liver disease (MASLD).
The Study of the Inheritance Mechanisms of Myotonic Dystrophy Type 1 (DM1) in Families from the Republic of North Ossetia-Alania
Authors: Ionova Sofya A. , Murtazina Aysylu F. , Marakhonov Andrey A. , Shchagina Olga A. , Ryadninskaya Nina V. , Tebieva Inna S. , Kadyshev Vitaly V. , Borovikov Artem O. , Ginter Evgeny K. , Kutsev Sergey I. , Zinchenko Rena A.
Published: September 2024

Myotonic dystrophy type 1 (DM1) is a multisystem disorder with progressive myopathy and myotonia. The clinical study was conducted in the Republic of North Ossetia-Alania (RNOA), and in it 39 individuals from 17 unrelated families were identified with DM1. Clinical presentations varied, including muscle weakness, fatigue, intellectual disability, hypersomnia, ophthalmological abnormalities, and alopecia. Using clinical and genotyping data, we confirmed the diagnosis and enabled the study of CTG-repeat anticipation and DM1 prevalence in the Ossetian and Ingush populations. CTG expansion correlated with age of onset, with clinical severity, and with offspring showing more severe symptoms than parents. In many families, the youngest child had a more severe DM1 phenotype than older siblings. The prevalence was 14.17 per 100,000 in Ossetians and 18.74 per 100,000 in Ingush people, aligning with global data. Segregation analysis showed a higher frequency of maternal transmission. The study highlights the clinical and genetic heterogeneity of DM1 and its dependence on repeat expansion and paternal and maternal age.
Comparative Analysis of the Mitochondrial Genome of Eggplant (Solanum melongena L.) to Identify Cytoplasmic Male Sterility Candidate Genes
Authors: Deng Wentao , Gan Guiyun , Li Weiliu , Yu Chuying , Jiang Yaqin , Li Die , Yang Qihong , Li Wenjia , Wang Peng , Wang Yikui
Published: September 2024

Cytoplasmic male sterility (CMS) is important for commercial hybrid seed production. However, it is still not used in eggplant (Solanum melongena L.), and corresponding regulatory genes and mechanisms of action have not been reported. We report CMS line 327A, which was derived from the hybridization between cultivated and wild eggplants. By looking at different stages of anther development under a microscope, we saw that the 327A anther’s tapetum layer vacuolized during meiosis, which caused abortion. To investigate the 327A CMS regulatory genes, the mitochondrial genomes of 327A and its maintainer line 327B were assembled de novo. It was found that 15 unique ORFs (Open Reading Frame) were identified in 327A. RT-PCR and RT-QPCAR tests confirmed that orf312a and orf172a, 327A-specific ORFs with a transmembrane domain, were strongly expressed in sterile anthers of 327A. In addition, orf312a has a chimeric structure with the ribosomal protein subunit rpl16. Therefore, orf312a and orf172a can be considered strong candidate genes for CMS. Concurrently, we analyzed the characteristics of CMS to develop a functional molecular marker, CMS312, targeting a future theoretical basis for eggplant CMS three-line molecular breeding.
Synthesis of Ethyl Pyrimidine-Quinolincarboxylates Selected from Virtual Screening as Enhanced Lactate Dehydrogenase (LDH) Inhibitors
Authors: Díaz Iván , Salido Sofía , Nogueras Manuel , Cobo Justo
Published: September 2024

The inhibition of the hLDHA (human lactate dehydrogenase A) enzyme has been demonstrated to be of great importance in the treatment of cancer and other diseases, such as primary hyperoxalurias. In that regard, we have designed, using virtual docking screening, a novel family of ethyl pyrimidine-quinolinecarboxylate derivatives (13–18)(a–d) as enhanced hLDHA inhibitors. These inhibitors were synthesised through a convergent pathway by coupling the key ethyl 2-aminophenylquinoline-4-carboxylate scaffolds (7–12), which were prepared by Pfitzinger synthesis followed by a further esterification, to the different 4-aryl-2-chloropyrimidines (VIII(a–d)) under microwave irradiation at 150–170 °C in a green solvent. The values obtained from the hLDHA inhibition were in line with the preliminary of the preliminary docking results, the most potent ones being those with U-shaped disposition. Thirteen of them showed IC50 values lower than 5 μM, and for four of them (16a, 18b, 18c and 18d), IC50 ≈ 1 μM. Additionally, all compounds with IC50 < 10 μM were also tested against the hLDHB isoenzyme, resulting in three of them (15c, 15d and 16d) being selective to the A isoform, with their hLDHB IC50 > 100 μM, and the other thirteen behaving as double inhibitors.
Impact of Methylated Cyclodextrin KLEPTOSE® CRYSMEB on Inflammatory Responses in Human In Vitro Models
Authors: Truffin Damien , Marchand Flora , Chatelais Mathias , Chêne Gérald , Saias Laure , Herbst Frauke , Lipner Justin , King Alastair J.
Published: September 2024

KLEPTOSE® CRYSMEB methylated cyclodextrin derivative displays less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases, linked in part to cholesterol complexation and immune response, however, its impact on inflammatory cascade pathways is not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells under physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® panel. Finally, its anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects that were driven by the inhibition of pro-inflammatory cytokine secretion and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Additionally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by other well-known anti-inflammatory molecules. Finally, KLEPTOSE® CRYSMEB may have an anti-inflammatory impact, which could be due to its effect on receptors such as TLR or direct complexation with LPS or PGE2, and conversely, this methylated cyclodextrin could stimulate a pro-inflammatory response involving lipid mediators and on proteins involved in communication with immune cells, probably via interaction with membrane cholesterol.
The Impact of ARMS2 (rs10490924), VEGFA (rs3024997), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), and IL1B1 (rs1143623) Polymorphisms and Serum Levels on Age-Related Macular Degeneration Development and Therapeutic Responses
Authors: Cebatoriene Dzastina , Vilkeviciute Alvita , Gedvilaite-Vaicechauskiene Greta , Duseikaite Monika , Bruzaite Akvile , Kriauciuniene Loresa , Zaliuniene Dalia , Liutkeviciene Rasa
Published: September 2024

Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective but do not respond optimally in all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the ARMS2 (rs10490924), IL1B1 (rs1143623), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), VEGFA (rs3024997), ARMS2, IL1B1, TNFRSF1B, TNFRSF1A, and VEGFA serum levels in AMD development and treatment efficacy. This study examined the associations of specific genetic polymorphisms and serum protein levels with exudative and early AMD and the response to anti-VEGF treatment. The AA genotype of VEGFA (rs3024997) was significantly associated with a 20-fold reduction in the odds of exudative AMD compared to the GG + GA genotypes. Conversely, the TT genotype of ARMS2 (rs10490924) was linked to a 4.2-fold increase in the odds of exudative AMD compared to GG + GT genotypes. In females, each T allele of ARMS2 increased the odds by 2.3-fold, while in males, the TT genotype was associated with a 5-fold increase. Lower serum IL1B levels were observed in the exudative AMD group compared to the controls. Early AMD patients had higher serum TNFRSF1B levels than controls, particularly those with the GG genotype of TNFRSF1B rs1061622. Exudative AMD patients with the CC genotype of TNFRSF1A rs4149576 had lower serum TNFRSF1A levels compared to the controls. Visual acuity (VA) analysis showed that non-responders had better baseline VA than responders but experienced decreased VA after treatment, whereas responders showed improvement. Central retinal thickness (CRT) reduced significantly in responders after treatment and was lower in responders compared to non-responders after treatment. The T allele of TNFRSF1B rs1061622 was associated with a better response to anti-VEGF treatment under both dominant and additive genetic models. These findings highlight significant genetic and biochemical markers associated with AMD and treatment response. This study found that the VEGFA rs3024997 AA genotype reduces the odds of exudative AMD, while the ARMS2 rs10490924 TT genotype increases it. Lower serum IL1B levels and variations in TNFRSF1B and TNFRSF1A levels were linked to AMD. The TNFRSF1B rs1061622 T allele was associated with better anti-VEGF treatment response. These markers could potentially guide risk assessment and personalized treatment for AMD.
Prostate-Specific Membrane Antigen Biology and Pathophysiology in Prostate Carcinoma, an Update: Potential Implications for Targeted Imaging and Therapy
Authors: Maes Justine , Gesquière Simon , De Spiegeleer Anton , Maes Alex , Van de Wiele Christophe
Published: September 2024

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, was shown to be expressed 100–1000 fold higher in prostate adenocarcinoma as compared to normal prostate epithelium. Given the enzymatic function of PSMA with the presence of an internalization triggering motif, various Glu-urea-Lys-based inhibitors have been developed and, amongst others, radiolabeled with positron emitters for targeted positron emission tomography imaging such as 68Ga-PSMA-HBED-CC Glu-urea-Lys(Ahx) as well as with beta and alpha-emitting radioisotopes for targeted therapy, e.g., 177Lu-PSMA-617. In this paper, we review and discuss the potential implications for targeted imaging and therapy of altered PSMA-glycosylation, of PSMA-driven activation of the P13K/Akt/mTOR, of the evolution over time and the relationship with androgen signaling and changes in DNA methylation of PSMA, and of androgen deprivation therapy (ADT) in prostate carcinoma.
Application of PS-InSAR and Diagnostic Train Measurement Techniques for Monitoring Subsidence in High-Speed Railway in Konya, Türkiye
Authors: Kizilirmak Gokhan , Cakir Ziyadin
Published: September 2024

Large-scale man-made linear structures like high-speed railway lines have become increasingly important in modern life as a faster and more comfortable transportation option. Subsidence or longitudinal levelling deformation problems along these railway lines can prevent the line from operating effectively and, in some cases, require speed reduction, continuous maintenance or repairs. In this study, the longitudinal levelling deformation of the high-speed railway line passing through Konya province (Central Turkey) was analyzed for the first time using the Persistent Scatter Synthetic Aperture Radar Interferometry (PS-InSAR) technique in conjunction with diagnostic train measurements, and the correlation values between them were found. In order to monitor potential levelling deformation along the railway line, medium-resolution, free-of-charge C-band Sentinel-1 (S-1) data and high-resolution, but paid, X-band Cosmo-SkyMed (CSK) Synthetic Aperture Radar (SAR) data were analyzed from the diagnostic train and reports received from the relevant maintenance department. Comparison analyses of the results obtained from the diagnostic train and radar measurements were carried out for three regions with different deformation scenarios, selected from a 30 km railway line within the whole analysis area. PS-InSAR measurements indicated subsidence events of up to 40 mm/year along the railway through the alluvial sediments of the Konya basin, which showed good agreement with the diagnostic train. This indicates that the levelling deformation of the railway and its surroundings can be monitored efficiently, rapidly and cost-effectively using the InSAR technique.
Influence of Road Infrastructure Design over the Traffic Accidents: A Simulated Case Study
Authors: Dumitrascu Dorin-Ion
Published: September 2024

The influence of road infrastructure over the severity of road accidents, in particular some specific features of it, represents the subject of this study. Generally, when an accident occurs, its causes are represented by a number of factors such as driver experience, fatigue, driving under the influence of alcohol and other psychoactive substances, road configuration, weather conditions, speeding, distracted driving, and unsafe road infrastructure. Road design is a key factor regarding the safety of all traffic participants. In this paper, the influence of unsafe roadside element designs on the incidence of traffic accidents, the degree of vehicle passenger injury, and the level of car damage were investigated. The present study was inspired by the high number of accidents produced on European route E68 (DN1) in Romania, a significant part of which was generated and accentuated by the effects of improper roadside design.
Deep Learning for Pavement Condition Evaluation Using Satellite Imagery
Authors: Lebaku Prathyush Kumar Reddy , Gao Lu , Lu Pan , Sun Jingran
Published: September 2024

Civil infrastructure systems cover large land areas and need frequent inspections to maintain their public service capabilities. Conventional approaches of manual surveys or vehicle-based automated surveys to assess infrastructure conditions are often labor-intensive and time-consuming. For this reason, it is worthwhile to explore more cost-effective methods for monitoring and maintaining these infrastructures. Fortunately, recent advancements in satellite systems and image processing algorithms have opened up new possibilities. Numerous satellite systems have been employed to monitor infrastructure conditions and identify damages. Due to the improvement in the ground sample distance (GSD), the level of detail that can be captured has significantly increased. Taking advantage of these technological advancements, this research evaluated pavement conditions using deep learning models for analyzing satellite images. We gathered over 3000 satellite images of pavement sections, together with pavement evaluation ratings from the TxDOT’s PMIS database. The results of our study show an accuracy rate exceeding 90%. This research paves the way for a rapid and cost-effective approach for evaluating the pavement network in the future.