bluuebunny/crossref_metadata_2025 huggingface dataset:
The Seismic Resistance Analysis of Frame Structures and Wall Structures Using Ferrocement and Expanded Metal
Authors: Chonratana Yossakorn , Chatpattananan Vuttichai
Published: April 2023

This article presents a study of the use of ferrocement and expanded metal in the columns, beams, and walls of a reinforced concrete building structure to increase its seismic resistance. This study focused on a concrete building with three stories, located in Thailand. In the design of the reinforcement structure, a calculation and analysis of seismic resistance were conducted in a comparison of the original concrete building structure with the reinforced concrete building structure using the nonlinear static force method (pushover analysis method). The results showed that the seismic resistance of the reinforced concrete building structure was higher than the design value (DPT), with different seismic resistance values for the reinforced frames, columns, and walls of approximately 14%, 81%, and 19%. In particular, it had increased stiffness values for the frames, columns, and walls and increased ductility values for the walls. Moreover, the seismic resistance values originating from the reinforcement were significantly higher than those of the concrete building structure. Therefore, reinforcement should be applied to all concrete building structures with the implementation of the damage index, ensuring that it is reduced to the allowable level.
Applications of Serious Games as Affective Disorder Therapies in Autistic and Neurotypical Individuals: A Literature Review
Authors: Ahmed Fahad , Requena Carrión Jesús , Bellotti Francesco , Barresi Giacinto , Floris Federica , Berta Riccardo
Published: April 2023

Affective disorders can greatly influence the everyday lives of neurotypical and autistic individuals. As platforms that promote engagement, computer-based serious games (CSGs) have been previously proposed as therapies to treat affective disorders for both populations. However, these CSGs were assessed on a wide variety of experimental conditions, and there is a lack of comparative studies on their effectiveness. In this study, we identified and analyzed 37 interventions of CSGs for affective disorders in autistic and neurotypical individuals from 507 initial search results from four databases (Embase, Scopus, Web Of Science and IEEE Xplore), using concepts such as ‘serious-games’, ‘affective-disorders’, ‘autism’ and ‘neurotypical’. A total of 21 different CSGs were identified that were evaluated with 30 different outcome measures in the reviewed interventions. A positive impact was reported in 22 of them; specifically, all instances of depression interventions reported a positive impact of CSG therapies. Our comparative analysis indicates that CSG applications could be effective in treating affective disorders in autistic and neurotypical individuals. Additionally, our analysis identifies CSG design characteristics that might be useful in applications involving depression, anxiety and phobias. Based on these characteristics, we provide a set of recommendations for CSG interventions for affective disorder therapies.
Gloss-Bridge: A Method to Reduce the Visual Perception Gap between Real-World Glossiness and PBR Reflectance Properties in Virtual Reality
Authors: Xiao Weiye , Tan Taoyong , Xue Chengqi
Published: April 2023

With the rapid development of virtual reality (VR) technology, digital materials have become more realistic and controllable, offering new opportunities for material perception research. However, material parameters for physically based rendering (PBR), which are widely used in industry, are often derived from design experience and lack interpretability. This study aims to investigate the visual perception difference of material glossiness between real and virtual environments. A compensation method is proposed to bridge the glossiness perception gap between the real-world and PBR. Two psychophysical experiments are conducted. Experiment 1 measures the psychological perception of materials with different glossiness in the real world and VR using a two-alternative forced-choice (2AFC) design. Experiment 2 establishes a connection between multiple parameters in PBR and the psychologically perceived glossiness obtained in Experiment 1 through a material matching adjustment experiment. Finally, a material glossiness mapping method for VR real-time rendering, Gloss-Bridge, is introduced. This method maps the physical quantity (measured by gloss meter) to various PBR parameters. By using physical parameters instead of empirical parameters, it eliminates tedious hyper-parameter adjustments. This achievement provides a design basis for the production of VR materials based on subjective perception and physical parameters.
Study of Copper/Aluminum Bimetallic Tube Rotary Ring Spinning Composite Forming Characteristics
Authors: Wang Chen , Zhang Binkai , Yao Dongfang , Tian Zhuangzhuang , Zhao Chunjiang
Published: April 2023

As a plastic forming process developed based on rotary wheel spinning technology, the rotary ring spinning process has the excellent characteristics of high forming accuracy and high material utilization rate, and has been gradually applied to the manufacture of bimetallic composite pipes. In this paper, the forming law of a bimetallic tube in the process of rotary ring spinning was analyzed by numerical simulation and experimentation. The results show that the deformation coordination of the basic and cover tubes increased with the increasing press amount, and the feed ratio had less of an effect on the thickness variation. In addition, the three-way strain of the basic and cover tubes and the degree of influence of the process parameters on the equivalent strain of the tubes were also studied. The results show that the radial strain on both tubes was the largest, followed by the axial strain, and the tangential strain was the smallest; the press amount had the largest effect on the equivalent strain of the tubes, followed by the angle of attack and the feed ratio. These results provide some guidance for the manufacture of high-performance bimetallic composite tubes by rotary ring spinning.
Optimization of Aggregate Characteristic Parameters for Asphalt Binder—Aggregate System under Moisture Susceptibility Condition Based on Random Forest Analysis Model
Authors: Cao Shenyang , Li Ping , Nan Xueli , Yi Zhao , Sun Mengkai
Published: April 2023

Water damage to asphalt pavements is a common occurrence that lowers the quality of service they can offer and causes several traffic problems. The loss of adhesion characteristics in the system of the asphalt binder and aggregate is the primary source of the problem of water damage in asphalt mixes. A number of things, including the impact of aggregate characteristics on asphalt binder—aggregate systems’ adhesion characteristics, have been proven. Through the use of random forest analysis, this study seeks to maximize the screening of aggregate characteristic factors. In this research, the morphology characterization, chemical composition, and phase composition of the five aggregates were first studied, and their relevant characteristic parameters were calculated. A method of engineering evaluation of the resistance of asphalt mixtures to water damage was used to assess the water susceptibility of the five asphalt binder—aggregate systems. Next, utilizing the fuzzy comprehensive evaluation analysis approach, a thorough study of the water susceptibility of the five asphalt binder—aggregate systems was conducted. Finally, sensitivity analysis of the aggregate characteristic parameters was carried out by a random forest analysis model, so as to achieve the optimal screening of the aggregate characteristic parameters. The results showed that, during sensitivity analysis of each parameter of aggregate properties using random forest analysis, the SiO2 content of the aggregate had the highest importance, and the roughness had the highest importance among the morphology characterizations. The water susceptibility of the asphalt binder—aggregate system could be expressed by the SiO2 content and roughness of the aggregate characteristic parameters.
Method for Training and White Boxing DL, BDT, Random Forest and Mind Maps Based on GNN
Authors: Arai Kohei
Published: April 2023

A method for training and white boxing of deep learning (DL) binary decision trees (BDT), random forest (RF) as well as mind maps (MM) based on graph neural networks (GNN) is proposed. By representing DL, BDT, RF, and MM as graphs, these can be trained by GNN. These learning architectures can be optimized through the proposed method. The proposed method allows representation of the architectures with matrices because the learning architecture can be expressed with graphs. These matrices and graphs are visible, which makes the learning processes visible, and therefore, more accountable. Some examples are shown here to highlight the usefulness of the proposed method, in particular, for learning processes and for ensuring the accountability of DL together with improvement in network architecture.
Analysis on the Spatial-Temporal Distribution Patterns of Major Mine Debris Flows in China
Authors: Ye Tianhao , Wang Guangjin , Wang Chunlai , Chen Hui , Xin Yingming
Published: April 2023

In order to provide more accurate data support for the prevention and control of geological disasters in mines, the article counts the major mine debris flow accidents in China from 1954 to 2019; studies the distribution of debris flow disasters in each province; reveals the intra-annual and inter-annual variation patterns of the number of mine debris flow disasters; analyzes the distribution of mine debris flows under different geoenvironmental backgrounds; and combines AHP hierarchical analysis with a comprehensive regional evaluation of the likelihood of mine debris flows. The results of the study show that from 1954 to 2019, the number of major mine debris flow disasters first increased and then decreased. The proportion of mine debris flow disasters to the total number of debris flow disasters also showed a trend of first increasing and then decreasing, with the southwestern region being the area of high occurrence of mine debris flow, and the geoenvironmental areas of middle and low hills and middle and high mountains being the topographic areas of high occurrence of mine debris flow. More than 90% of the major mine debris flow disasters occurred from May to September, with the largest number of disasters occurring in July. A comprehensive evaluation of the regional nature of mine debris flow distribution based on the regional evaluation score is derived.
The Holy See and Fyodor Dostoevsky: Mutual Attraction and Repulsion
Authors: Besschetnova Elena
Published: April 2023

The article analyzes the attitude of Fyodor Dostoevsky toward the Roman Catholic Church. The author shows how Dostoevsky comes to the Slavophile idea of unity and the impossibility of salvation outside church communion, while speaking of the Church as an ecclesia, that is, an assembly of believers. At the same time, the reception of Dostoevsky from the side of the Vatican is presented. In the article, special attention is paid to the perception of Dostoevsky’s ideas by Pope Francis. The author notes that the point of attraction and repulsion between Dostoevsky and Catholic culture lies in the plane of his understanding of the concepts of nationality and universality. Dostoevsky’s Russian idea and his view on the essence of Christianity grows from the synthesis of these concepts. The author emphasizes that only in this perspective it is necessary to interpret Dostoevsky’s ideas.
Indigenisation of the Quantum Clock: An Indispensable Tool for Modern Technologies
Authors: De Subhadeep , Sharma Arijit
Published: April 2023

Time and frequency (T&F) measurement with unprecedented accuracy is the backbone for several sophisticated technologies, commensurate with the evolution of human civilisation in the 20th century in terms of communication, positioning, navigation, and precision timing. This necessity drove researchers in the early 1950s to build atomic clocks that have now evolved to a state-of-the-art level, operating at optical wavelengths as optical atomic clocks, which use cold and trapped samples of atomic/ionic species and various other sophisticated diagnostic test techniques. Such ultrahigh-precision accurate clocks have made it possible to probe fundamental aspects of science through incredibly sensitive measurements. On the other hand, they meet the T&F synchronisation standards for classical and emerging quantum technologies at the desired level of accuracy. Considering the impact of optical atomic clocks in the second quantum revolution (quantum 2.0), they have been identified as an indispensable critical technology in worldwide quantum missions, including in India. This article reviews the present international scenario regarding optical atomic clocks and their related technologies and draws a roadmap for their indigenisation over the next decade.
Coefficient Results concerning a New Class of Functions Associated with Gegenbauer Polynomials and Convolution in Terms of Subordination
Authors: Olatunji Sunday Olufemi , Oluwayemi Matthew Olanrewaju , Oros Georgia Irina
Published: April 2023

Gegenbauer polynomials constitute a numerical tool that has attracted the interest of many function theorists in recent times mainly due to their real-life applications in many areas of the sciences and engineering. Their applications in geometric function theory (GFT) have also been considered by many researchers. In this paper, this powerful tool is associated with the prolific concepts of convolution and subordination. The main purpose of the research contained in this paper is to introduce and study a new subclass of analytic functions. This subclass is presented using an operator defined as the convolution of the generalized distribution and the error function and applying the principle of subordination. Investigations into this subclass are considered in connection to Carathéodory functions, the modified sigmoid function and Bell numbers to obtain coefficient estimates for the contained functions.
A Multi-Stage Adaptive Method for Remaining Useful Life Prediction of Lithium-Ion Batteries Based on Swarm Intelligence Optimization
Authors: Bao Qihao , Qin Wenhu , Yun Zhonghua
Published: April 2023

The accuracy of predicting the remaining useful life of lithium batteries directly affects the safe and reliable use of the supplied equipment. Since the degradation of lithium batteries can easily be influenced by different operating conditions and the regeneration and fluctuation of battery capacity during the use of lithium batteries, it is difficult to construct an accurate prediction model of lithium batteries. Therefore, research into high-precision methods of predicting the remaining useful life has been a popular topic for the whole-life management system of lithium batteries. In this paper, a new hybrid optimization method for predicting the remaining useful life of lithium batteries is proposed. The proposed method incorporates two different swarm intelligence optimization algorithms. Firstly, the whale optimization algorithm is used to optimize the variational mode decomposition (WOAVMD), which can decompose the historical life data into several trend components and non-trend components. Then, the sparrow search algorithm is applied to optimize the long short-term memory neural network (SSALSTM) to predict the non-trend component and the autoregressive integrated moving average model (ARIMA) is used to predict trend components. Finally, the prediction results of each component are integrated to evaluate the remaining useful life of lithium batteries. Results show that better prediction accuracy is obtained in the prediction experiments for several types of batteries in both the NASA and CALCE battery datasets. The generalization ability of the algorithm has also been effectively improved owing to the optimization of parameters of the variational mode decomposition (VMD) and the long short-term memory neural network (LSTM).
Electrical Stimulation in Cartilage Tissue Engineering
Authors: Vaiciuleviciute Raminta , Uzieliene Ilona , Bernotas Paulius , Novickij Vitalij , Alaburda Aidas , Bernotiene Eiva
Published: April 2023

Electrical stimulation (ES) has been frequently used in different biomedical applications both in vitro and in vivo. Numerous studies have demonstrated positive effects of ES on cellular functions, including metabolism, proliferation, and differentiation. The application of ES to cartilage tissue for increasing extracellular matrix formation is of interest, as cartilage is not able to restore its lesions owing to its avascular nature and lack of cells. Various ES approaches have been used to stimulate chondrogenic differentiation in chondrocytes and stem cells; however, there is a huge gap in systematizing ES protocols used for chondrogenic differentiation of cells. This review focuses on the application of ES for chondrocyte and mesenchymal stem cell chondrogenesis for cartilage tissue regeneration. The effects of different types of ES on cellular functions and chondrogenic differentiation are reviewed, systematically providing ES protocols and their advantageous effects. Moreover, cartilage 3D modeling using cells in scaffolds/hydrogels under ES are observed, and recommendations on reporting about the use of ES in different studies are provided to ensure adequate consolidation of knowledge in the area of ES. This review brings novel insights into the further application of ES in in vitro studies, which are promising for further cartilage repair techniques.
Characterization of Biocompatibility of Functional Bioinks for 3D Bioprinting
Authors: Kim Jinku
Published: April 2023

Three-dimensional (3D) bioprinting with suitable bioinks has become a critical tool for fabricating 3D biomimetic complex structures mimicking physiological functions. While enormous efforts have been devoted to developing functional bioinks for 3D bioprinting, widely accepted bioinks have not yet been developed because they have to fulfill stringent requirements such as biocompatibility and printability simultaneously. To further advance our knowledge of the biocompatibility of bioinks, this review presents the evolving concept of the biocompatibility of bioinks and standardization efforts for biocompatibility characterization. This work also briefly reviews recent methodological advances in image analyses to characterize the biocompatibility of bioinks with regard to cell viability and cell-material interactions within 3D constructs. Finally, this review highlights a number of updated contemporary characterization technologies and future perspectives to further advance our understanding of the biocompatibility of functional bioinks for successful 3D bioprinting.
Long-Term Effect of Diet Consistency on Mandibular Growth within Three Generations: A Longitudinal Cephalometric Study in Rats
Authors: Tsolakis Ioannis A. , Verikokos Christos , Papaioannou William , Alexiou Konstantina-Eleni , Yfanti Zafeiroula , Perrea Despoina , Tsolakis Apostolos I.
Published: April 2023

Background: This study investigated the effect of diet consistency on mandibular growth of Wistar rats through three generations. Methods: A total breeding sample of 60 female and 8 male Wistar rats were used in this study. Measurements took place only on female animals. Twenty female Wistar rats at 30 days old and four male rats at 30 days old comprised the primary breeding sample of the first generation, and from these animals two different generations were reproduced. Lateral cephalometric X-rays were taken from all female rats at the age of 100 days. A total of 7 craniofacial landmarks were selected for the linear measurements, and 12 curves and 90 landmarks were selected for geometric morphometric analysis of the lateral X-rays. Bonferroni test and a permutation test were performed for the statistical analysis. Results: Means of measurements of all soft diet groups compared to hard diet groups were significantly smaller. According to linear measurements, there was a significant difference only between the first-generation soft diet with the third-generation soft diet group. According to geometric morphometric analysis, the statistical differences appeared on the condylar process and the angle of the mandible. Conclusions: The soft diet could be responsible for less mandibular growth, and this information might be passing through generations.
Impacts of Deoxygenation and Hypoxia on Shark Embryos Anti-Predator Behavior and Oxidative Stress
Authors: Varela Jaquelino , Martins Sandra , Court Melanie , Santos Catarina Pereira , Paula José Ricardo , Ferreira Inês João , Diniz Mário , Repolho Tiago , Rosa Rui
Published: April 2023

Climate change is leading to the loss of oxygen content in the oceans and endangering the survival of many marine species. Due to sea surface temperature warming and changing circulation, the ocean has become more stratified and is consequently losing its oxygen content. Oviparous elasmobranchs are particularly vulnerable as they lay their eggs in coastal and shallow areas, where they experience significant oscillations in oxygen levels. Here, we investigated the effects of deoxygenation (93% air saturation) and hypoxia (26% air saturation) during a short-term period (six days) on the anti-predator avoidance behavior and physiology (oxidative stress) of small-spotted catshark (Scyliorhinus canicula) embryos. Their survival rate decreased to 88% and 56% under deoxygenation and hypoxia, respectively. The tail beat rates were significantly enhanced in the embryos under hypoxia compared to those exposed to deoxygenation and control conditions, and the freeze response duration showed a significant opposite trend. Yet, at the physiological level, through the analyses of key biomarkers (SOD, CAT, GPx, and GST activities as well as HSP70, Ubiquitin, and MDA levels), we found no evidence of increased oxidative stress and cell damage under hypoxia. Thus, the present findings show that the projected end-of-the-century deoxygenation levels elicit neglectable biological effects on shark embryos. On the other hand, hypoxia causes a high embryo mortality rate. Additionally, hypoxia makes embryos more vulnerable to predators, because the increased tail beat frequency will enhance the release of chemical and physical cues that can be detected by predators. The shortening of the shark freeze response under hypoxia also makes the embryos more prone to predation.
Expression Patterns of MiR-125a and MiR-223 and Their Association with Diabetes Mellitus and Survival in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Gager Gloria M. , Eyileten Ceren , Postuła Marek , Nowak Anna , Gąsecka Aleksandra , Jilma Bernd , Siller-Matula Jolanta M.
Published: April 2023

Background: MicroRNAs (miRNA, miR) are small, non-coding RNAs which have become increasingly relevant as diagnostic and prognostic biomarkers. The objective of this study was the investigation of blood-derived miRNAs and their link to long-term all-cause mortality in patients who suffered from non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: This study was an observational prospective study, which included 109 patients with NSTE-ACS. Analysis of the expression of miR-125a and miR-223 was conducted by polymerase chain reaction (PCR). The follow-up period comprised a median of 7.5 years. Long-term all-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events. Results: Increased expression of miR-223 (>7.1) at the time point of the event was related to improved long-term all-cause survival (adjusted (adj.) hazard ratio (HR) = 0.09, 95% confidence interval (95%CI): 0.01–0.75; p = 0.026). The receiver operating characteristic (ROC) analysis provided sufficient c-statistics (area under the curve (AUC) = 0.73, 95%CI: 0.58–0.86; p = 0.034; negative predictive value of 98%) for miR-223 to predict long-term all-cause survival. The Kaplan–Meier time to event analysis showed a separation of the survival curves between the groups at an early stage (log rank p = 0.015). Higher plasma miR-125a levels were found in patients with diabetes mellitus vs. in those without (p = 0.010). Furthermore, increased miR-125a expression was associated with an elevated HbA1c concentration. Conclusions: In this hypothesis-generating study, higher values of miR-223 were related to improved long-term survival in patients after NSTE-ACS. Larger studies are required in order to evaluate whether miR-223 can be used as a suitable predictor for long-term all-cause mortality.
A Comprehensive Review of the Genetic and Epigenetic Contributions to the Development of Fibromyalgia
Authors: Ovrom Erik A. , Mostert Karson A. , Khakhkhar Shivani , McKee Daniel P. , Yang Padao , Her Yeng F.
Published: April 2023

This narrative review summarizes the current knowledge of the genetic and epigenetic contributions to the development of fibromyalgia (FM). Although there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms.
The Relationship between Type 1 Diabetes Mellitus, TNF-α, and IL-10 Gene Expression
Authors: dos Santos Haber Jesselina Francisco , Barbalho Sandra Maria , Sgarbi Jose Augusto , de Argollo Haber Rafael Santos , de Labio Roger William , Laurindo Lucas Fornari , Chagas Eduardo Federighi Baisi , Payão Spencer Luiz Marques
Published: April 2023

Type 1 diabetes mellitus (T1DM) is one of the major chronic diseases in children worldwide. This study aimed to investigate interleukin-10 (IL-10) gene expression and tumor necrosis factor-alpha (TNF-α) in T1DM. A total of 107 patients were included, 15 were T1DM in ketoacidosis, 30 patients had T1DM and HbA1c ≥ 8%; 32 patients had T1DM and presented HbA1c < 8%; and 30 were controls. The expression of peripheral blood mononuclear cells was performed using the reverse transcriptase–polymerase chain reaction in real time. The cytokines gene expression was higher in patients with T1DM. The IL-10 gene expression increased substantially in patients with ketoacidosis, and there was a positive correlation with HbA1c. A negative correlation was found for IL-10 expression and the age of patients with diabetes, and the time of diagnosis of the disease. There was a positive correlation between TNF-α expression with age. The expression of IL-10 and TNF-α genes showed a significant increase in DM1 patients. Once current T1DM treatment is based on exogenous insulin, there is a need for other therapies, and inflammatory biomarkers could bring new possibilities to the therapeutic approach of the patients.
N-Carbamoylputrescine Amidohydrolase of Bacteroides thetaiotaomicron, a Dominant Species of the Human Gut Microbiota
Authors: Shimokawa Hiromi , Sakanaka Mikiyasu , Fujisawa Yuki , Ohta Hirokazu , Sugiyama Yuta , Kurihara Shin
Published: April 2023

Polyamines are bioactive amines that play a variety of roles, such as promoting cell proliferation and protein synthesis, and the intestinal lumen contains up to several mM polyamines derived from the gut microbiota. In the present study, we conducted genetic and biochemical analyses of the polyamine biosynthetic enzyme N-carbamoylputrescine amidohydrolase (NCPAH) that converts N-carbamoylputrescine to putrescine, a precursor of spermidine in Bacteroides thetaiotaomicron, which is one of the most dominant species in the human gut microbiota. First, ncpah gene deletion and complemented strains were generated, and the intracellular polyamines of these strains cultured in a polyamine-free minimal medium were analyzed using high-performance liquid chromatography. The results showed that spermidine detected in the parental and complemented strains was depleted in the gene deletion strain. Next, purified NCPAH-(His)6 was analyzed for enzymatic activity and found to be capable of converting N-carbamoylputrescine to putrescine, with a Michaelis constant (Km) and turnover number (kcat) of 730 µM and 0.8 s−1, respectively. Furthermore, the NCPAH activity was strongly (>80%) inhibited by agmatine and spermidine, and moderately (≈50%) inhibited by putrescine. This feedback inhibition regulates the reaction catalyzed by NCPAH and may play a role in intracellular polyamine homeostasis in B. thetaiotaomicron.
Recent Development of Nanomaterials for Transdermal Drug Delivery
Authors: Leong Moong Yan , Kong Yeo Lee , Burgess Kevin , Wong Won Fen , Sethi Gautam , Looi Chung Yeng
Published: April 2023

Nano-engineered medical products first appeared in the last decade. The current research in this area focuses on developing safe drugs with minimal adverse effects associated with the pharmacologically active cargo. Transdermal drug delivery, an alternative to oral administration, offers patient convenience, avoids first-pass hepatic metabolism, provides local targeting, and reduces effective drug toxicities. Nanomaterials provide alternatives to conventional transdermal drug delivery including patches, gels, sprays, and lotions, but it is crucial to understand the transport mechanisms involved. This article reviews the recent research trends in transdermal drug delivery and emphasizes the mechanisms and nano-formulations currently in vogue.
Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats
Authors: Karim Shahid , Madani Batoul , Burzangi Abdulhadi S. , Alsieni Mohammed , Bazuhair Mohammed A. , Jamal Maha , Daghistani Hussam , Barasheed Mohammed O. , Alkreathy Huda , Khan Mohammad Ahmed , Khan Lateef M.
Published: April 2023

Human colon microbiota produce a metabolite called urolithin A (URO A) from ellagic acid and linked compounds, and this metabolite has been demonstrated to have antioxidant, anti-inflammatory, and antiapoptotic activities. The current work examines the various mechanisms through which URO A protects against doxorubicin (DOX)-induced liver injury in Wistar rats. In this experiment, Wistar rats were administered DOX intraperitoneally (20 mg kg−1) on day 7 while given URO A intraperitoneally (2.5 or 5 mg kg−1 d−1) for 14 days. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) were measured. Hematoxylin and eosin (HE) staining was used to evaluate histopathological characteristics, and then antioxidant and anti-inflammatory properties were evaluated in tissue and serum, respectively. We also looked at how active caspase 3 and cytochrome c oxidase were in the liver. The findings demonstrated that supplementary URO A therapy clearly mitigated DOX-induced liver damage. The antioxidant enzymes SOD and CAT were elevated in the liver, and the levels of inflammatory cytokines, such as TNF-α, NF-kB, and IL-6, in the tissue were significantly attenuated, all of which complemented the beneficial effects of URO A in DOX-induced liver injury. In addition, URO A was able to alter the expression of caspase 3 and cytochrome c oxidase in the livers of rats that were subjected to DOX stress. These results showed that URO A reduced DOX-induced liver injury by reducing oxidative stress, inflammation, and apoptosis.
Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies
Authors: Ghosh Nilanjan , Chacko Leena , Bhattacharya Hiranmoy , Vallamkondu Jayalakshmi , Nag Sagnik , Dey Abhijit , Karmakar Tanushree , Reddy P. Hemachandra , Kandimalla Ramesh , Dewanjee Saikat
Published: April 2023

Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, in addition to apparent coronary heart disease, ischemia, and hypertension-related complications, has created a more challenging situation. Diabetes, as a predominant cardio-renal metabolic syndrome, is related to severe vascular risk factors, and it underlies various complex pathophysiological pathways at the metabolic and molecular level that progress and converge toward the development of diabetic cardiomyopathy (DCM). DCM involves several downstream cascades that cause structural and functional alterations of the diabetic heart, such as diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, and subsequent heart failure over time. The effects of glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular (CV) outcomes in diabetes have shown promising results, including improved contractile bioenergetics and significant cardiovascular benefits. The purpose of this article is to highlight the various pathophysiological, metabolic, and molecular pathways that contribute to the development of DCM and its significant effects on cardiac morphology and functioning. Additionally, this article will discuss the potential therapies that may be available in the future.
Genes and Microbiota Interaction in Monogenic Autoimmune Disorders
Authors: Costa Federica , Beltrami Eleonora , Mellone Simona , Sacchetti Sara , Boggio Elena , Gigliotti Casimiro Luca , Stoppa Ian , Dianzani Umberto , Rolla Roberta , Giordano Mara
Published: April 2023

Monogenic autoimmune disorders represent an important tool to understand the mechanisms behind central and peripheral immune tolerance. Multiple factors, both genetic and environmental, are known to be involved in the alteration of the immune activation/immune tolerance homeostasis typical of these disorders, making it difficult to control the disease. The latest advances in genetic analysis have contributed to a better and more rapid diagnosis, although the management remains confined to the treatment of clinical manifestations, as there are limited studies on rare diseases. Recently, the correlation between microbiota composition and the onset of autoimmune disorders has been investigated, thus opening up new perspectives on the cure of monogenic autoimmune diseases. In this review, we will summarize the main genetic features of both organ-specific and systemic monogenic autoimmune diseases, reporting on the available literature data on microbiota alterations in these patients.
Moderate-Intensity Exercise Improves Mesenteric Arterial Function in Male UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) Rats: A Shift in the Relative Importance of Endothelium-Derived Relaxing Factors (EDRF)
Authors: Razan Md Rahatullah , Amissi Said , Islam Rifat Ara , Graham James L. , Stanhope Kimber L. , Havel Peter J. , Rahimian Roshanak
Published: April 2023

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric oxide (NO) synthase (eNOS), cyclooxygenase (COX), and calcium-activated potassium channel (KCa) channels were also measured. T2DM significantly impaired EDV, increased contractile responses and myogenic tone. The impairment of EDV was accompanied by elevated NO and COX importance, whereas the contribution of prostanoid- and NO-independent (endothelium-derived hyperpolarization, EDH) relaxation was not apparent compared to controls. MIE 1) enhanced EDV, while it reduced contractile responses, myogenic tone and systolic blood pressure (SBP), and 2) caused a shift away from a reliance on COX toward a greater reliance on EDH in diabetic arteries. We provide the first evidence of the beneficial effects of MIE via the altered importance of EDRF in mesenteric arterial relaxation in male UCD-T2DM rats.
Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy
Authors: Műzes Györgyi , Sipos Ferenc
Published: April 2023

The immune system and autophagy share a functional relationship. Both innate and adaptive immune responses involve autophagy and, depending on the disease’s origin and pathophysiology, it may have a detrimental or positive role on autoimmune disorders. As a “double-edged sword” in tumors, autophagy can either facilitate or impede tumor growth. The autophagy regulatory network that influences tumor progression and treatment resistance is dependent on cell and tissue types and tumor stages. The connection between autoimmunity and carcinogenesis has not been sufficiently explored in past studies. As a crucial mechanism between the two phenomena, autophagy may play a substantial role, though the specifics remain unclear. Several autophagy modifiers have demonstrated beneficial effects in models of autoimmune disease, emphasizing their therapeutic potential as treatments for autoimmune disorders. The function of autophagy in the tumor microenvironment and immune cells is the subject of intensive study. The objective of this review is to investigate the role of autophagy in the simultaneous genesis of autoimmunity and malignancy, shedding light on both sides of the issue. We believe our work will assist in the organization of current understanding in the field and promote additional research on this urgent and crucial topic.
RAGE Inhibitors in Neurodegenerative Diseases
Authors: Reddy V. Prakash , Aryal Puspa , Soni Pallavi
Published: April 2023

Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer’s disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood–brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE–RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE–RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE–RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.
Targeting RNA Polymerase I Transcription Activity in Osteosarcoma: Pre-Clinical Molecular and Animal Treatment Studies
Authors: Kang Chang-Won , Blackburn Anneke C. , Loh Amos Hong Pheng , Hong Kuick Chick , Goh Jian Yuan , Hein Nadine , Drygin Denis , Parish Chris R. , Hannan Ross D. , Hannan Katherine M. , Coupland Lucy A.
Published: April 2023

The survival rate of patients with osteosarcoma (OS) has not improved over the last 30 years. Mutations in the genes TP53, RB1 and c-Myc frequently occur in OS and enhance RNA Polymerase I (Pol I) activity, thus supporting uncontrolled cancer cell proliferation. We therefore hypothesised that Pol I inhibition may be an effective therapeutic strategy for this aggressive cancer. The Pol I inhibitor CX-5461 has demonstrated therapeutic efficacy in different cancers in pre-clinical and phase I clinical trials; thus, the effects were determined on ten human OS cell lines. Following characterisation using genome profiling and Western blotting, RNA Pol I activity, cell proliferation and cell cycle progression were evaluated in vitro, and the growth of TP53 wild-type and mutant tumours was measured in a murine allograft model and in two human xenograft OS models. CX-5461 treatment resulted in reduced ribosomal DNA (rDNA) transcription and Growth 2 (G2)-phase cell cycle arrest in all OS cell lines. Additionally, tumour growth in all allograft and xenograft OS models was effectively suppressed without apparent toxicity. Our study demonstrates the efficacy of Pol I inhibition against OS with varying genetic alterations. This study provides pre-clinical evidence to support this novel therapeutic approach in OS.
Influence of Various Light Regimes on Morphofunctional Condition of Transplantable Melanoma B16
Authors: Areshidze David A. , Kozlova Maria A. , Mnikhovich Maxim V. , Bezuglova Tatyana V. , Chernikov Valery P. , Gioeva Zarina V. , Borisov Aleksey V.
Published: April 2023

A study of the morphofunctional condition of mice with transplantable melanoma B16 under the influence of a normal daylight regime, constant lighting and constant darkness was conducted. It was shown that exposure to constant lighting leads to intensification of the proliferation of melanoma cells, more significant growth and spread of the tumor, the development of more pronounced secondary changes, the presence of perivascular growth and an increase in perineural invasion. At the same time, keeping of animals in constant darkness significantly reduced the intensity of the proliferative process in the tumor and lead to tumor regression in the absence of signs of lympho-, intravascular and intraneural invasion. Intergroup differences in tumor cell status were confirmed by the results of micromorphometric studies. It was also shown that the expression of clock genes was suppressed by an exposure to constant light, while an influence of constant darkness, on contrary, led to its intensification.
Anti-microRNA-1976 as a Novel Approach to Enhance Chemosensitivity in XAF1+ Pancreatic and Liver Cancer
Authors: Lee Tsai-Yen , Tseng Chien-Jen , Wang Jin-Wun , Wu Ching-Po , Chung Chin-Yuan , Tseng Ting-Ting , Lee Shao-Chen
Published: April 2023

The current cancer treatments using chemoagents are not satisfactory in terms of outcomes and prognosis. Chemoagent treatments result in cell death or arrest, but the accompanying cellular responses are not well-studied. Exosomes, which are extracellular vesicles secreted by living cells, might mediate cellular responses through microRNAs. We found that miR-1976 was highly enriched in exosomes secreted after chemoagent treatment. We developed a novel approach for in situ mRNA target screening and discovered several miR-1976-specific mRNA targets, including the proapoptotic gene XAF1, which was targeted by miR-1976 and which suppressed chemoagent-induced cell apoptosis. Increased RPS6KA1 gene transcription was associated with the increase in its intronic pre-miR-1976 expression. Blockade of miR-1976 could enhance chemosensitivities of hepatoma and pancreatic cancer cells in an XAF1-dependent manner, as evidenced by increased levels of cell apoptosis, reduced IC50 in cell toxicity assays, and suppressed tumor growth in animal xenograft experiments in vivo. We propose that intracellular levels of miR-1976 determine chemosensitivity, and its blockade could be a novel strategy and potential therapeutic application in cancer treatment.
Catecholaminergic and Cholinergic Systems Mediate Beneficial Effect of Vortioxetine on Diabetes-Induced Neuropathic Pain
Authors: Turan Yücel Nazlı , Kandemir Ümmühan , Üçel Umut İrfan , Demir Özkay Ümide , Can Özgür Devrim
Published: April 2023

The therapeutic potential of vortioxetine on mechanical hyperalgesia/allodynia was investigated in rats with streptozotocin-induced diabetes, and its possible mechanism of action was elucidated in this study. The obtained findings demonstrated that subacute vortioxetine treatment (5 and 10 mg/kg for 2 weeks) increased the reduced paw-withdrawal thresholds of diabetic rats both in the Randall–Selitto and Dynamic plantar tests. Moreover, the falling latencies of animals did not change in the Rota-rod assessments. These results suggest that vortioxetine administration significantly improved diabetes-induced hyperalgesia and allodynia responses in the rats without affecting their motor coordination. The vortioxetine (5 mg/kg)-induced antihyperalgesic and antiallodynic effects were reversed by AMPT, yohimbine, ICI 118,551, sulpiride and atropine pre-treatments, suggesting the involvement of the catecholaminergic system, α2- and β2-adrenoceptors, D2/3 dopaminergic receptors and cholinergic muscarinic receptors in the exhibited pharmacological activity, respectively. Moreover, the data from the immunohistochemical studies indicated that the inhibition of c-Fos overexpression in dorsal horn neurons also mediates the beneficial effect of this drug. Vortioxetine induced no difference in plasma glucose levels in diabetic rats. If clinical studies confirm these findings, the concomitant beneficial effect of vortioxetine on mood disorders and its neutral activity profile on glycemic control may make it an alternative drug for the treatment of neuropathic pain.
Artificial Intelligence in Acute Ischemic Stroke Subtypes According to Toast Classification: A Comprehensive Narrative Review
Authors: Miceli Giuseppe , Basso Maria Grazia , Rizzo Giuliana , Pintus Chiara , Cocciola Elena , Pennacchio Andrea Roberta , Tuttolomondo Antonino
Published: April 2023

The correct recognition of the etiology of ischemic stroke (IS) allows tempestive interventions in therapy with the aim of treating the cause and preventing a new cerebral ischemic event. Nevertheless, the identification of the cause is often challenging and is based on clinical features and data obtained by imaging techniques and other diagnostic exams. TOAST classification system describes the different etiologies of ischemic stroke and includes five subtypes: LAAS (large-artery atherosclerosis), CEI (cardio embolism), SVD (small vessel disease), ODE (stroke of other determined etiology), and UDE (stroke of undetermined etiology). AI models, providing computational methodologies for quantitative and objective evaluations, seem to increase the sensitivity of main IS causes, such as tomographic diagnosis of carotid stenosis, electrocardiographic recognition of atrial fibrillation, and identification of small vessel disease in magnetic resonance images. The aim of this review is to provide overall knowledge about the most effective AI models used in the differential diagnosis of ischemic stroke etiology according to the TOAST classification. According to our results, AI has proven to be a useful tool for identifying predictive factors capable of subtyping acute stroke patients in large heterogeneous populations and, in particular, clarifying the etiology of UDE IS especially detecting cardioembolic sources.
Advances in Pathogenesis and Therapeutics of Hepatobiliary Diseases
Authors: Wang Jing-Hua
Published: April 2023

The hepatobiliary system, comprising the liver, gallbladder, and bile ducts, performs a diverse array of functions that are essential to maintaining homeostasis [...]