Multidisciplinary Digital Publishing Institute (Switzerland)
Multidisciplinary Digital Publishing InstituteNot a member yet
1861300 research outputs found
Sort by
Small Interfering RNA (siRNA) as a Targeted Therapy for Acute Respiratory Distress Syndrome: Evidence from Experimental Models
No full textAcute Respiratory Distress Syndrome (ARDS) is a severe complication of acute lung injury (ALI) characterized by acute hypoxemic respiratory failure and diffuse alveolar damage, with a high mortality rate and a current lack of treatments beyond supportive care. Its complex pathophysiology involves immune cell activation, pro-inflammatory cytokine release, and disruption of the alveolar–capillary barrier, leading to pulmonary edema and fibrosis. This review explores the potential of small interfering RNA (siRNA) therapy as a novel pathogenetic treatment for ARDS. The mechanism of RNA interference is described, highlighting its high specificity for silencing target genes. The paper then evaluates various animal models used in ARDS preclinical research, noting the advantages of large animals (pigs) for their physiological similarity to humans and the suitability of rodents for studying long-term fibrotic stages. Finally, the review summarizes promising in vivo studies where siRNA-mediated knockdown of several genes (e.g., TIMP1, BTK, LCN2, HDAC7, CCL2, NOX4, TNFα and TLR4) significantly reduced inflammation, improved lung histology, and increased survival. The collective evidence underscores siRNA’s considerable potential for developing targeted therapies against ARDS, moving beyond symptomatic care to address the root molecular mechanisms of the disease
GLP-1 Receptor Agonist Exenatide Protects Against Doxorubicin-Induced Cardiotoxicity Through the SIRT1 Pathway: An Electrocardiographic, 99mTc-PYP Scintigraphic, and Biochemical Study
No full textBackground and Objectives: This study was designed to evaluate the potential cardioprotective effect of Exenatide against doxorubicin (DOX)-induced myocardial injury in rats by assessing scintigraphic alterations together with oxidative stress and inflammation. Materials and Methods: This study included 28 adult male Wistar albino rats that were randomized to 4 groups (n = 7): control, Exenatide alone, DOX (receiving DOX (18 mg/kg, i.p) on days 5–7; Exenatide + DOX (treated with Exenatide together with the DOX). On day 8, ECG, 99mTc-PYP scintigraphy, and biochemical parameters were evaluated. Results: DOX caused ECG abnormalities—bradycardia, significant QT prolongation, and elevated ST-segment amplitude—along with increased myocardial PYP uptake. Exenatide + DOX group significantly improved ECG changes. Biochemically, DOX markedly increased cardiac injury biomarkers (cTnT, CK, CK-MB), hepatic and renal injury markers (ALT, AST, LDH, BUN, creatinine), SIRT-1 level, inflammatory marker (NF-κB, TNF-α, IL-6, NO) and oxidative stress indicators (MDA, TOS), while decreasing antioxidant defenses (GSH, TAS, Nrf2). Exenatide co-treatment significantly attenuated all DOX-induced changes. Conclusions: Exenatide markedly attenuates DOX-induced cardiotoxicity by improving electrical conduction, reducing myocardial radiotracer uptake, and restoring oxidative–inflammatory balance through partial recovery of the SIRT-1/Nrf2/NF-κB pathway
In Vitro Hatching of Scylla paramamosain Embryos: Insights from Developmental and Transcriptomic Analyses
No full textScylla paramamosain is a commercially important crab species widely cultured in China. However, artificial breeding remains limited by the high mortality of ovigerous females and asynchronous embryo hatching. In vitro embryo hatching has emerged as a promising alternative, yet its practical feasibility and underlying molecular mechanisms have not been systematically investigated. In this study, we examined the developmental characteristics of S. paramamosain embryos under different temperature regimes and hatching modes, evaluated embryo viability following maternal death, and compared transcriptomic profiles of Zoea I larvae between in vitro and maternal hatching. Our results demonstrated that temperature had a pronounced effect on embryogenesis and survival, with 27–30 °C identified as the optimal range for development and hatching. Both low and high temperature extremes markedly reduced embryo survival. Developmental trajectories were largely comparable between in vitro and maternal hatching, confirming the reliability and feasibility of the in vitro approach. Embryos collected within 4 h after maternal death exhibited high hatching success, whereas those obtained after 8 h failed to hatch. Transcriptomic analysis revealed 3505 differentially expressed genes, including 1933 upregulated and 1572 downregulated, which were significantly enriched in pathways related to cell cycle regulation, energy metabolism, immune defense, and ion transport. These findings implied that in vitro embryos could maintain developmental competence by stabilizing genomic integrity, reallocating energy resources, and activating stress responsive mechanisms. This study provides the first comprehensive evidence supporting the feasibility of in vitro embryo hatching in S. paramamosain and offers practical insights for optimizing temperature regimes, improving the utilization of maternal resources, and advancing large scale seedstock production in crab aquaculture
SER-YOLOv8: An Early Forest Fire Detection Model Integrating Multi-Path Attention and NWD
No full textForest ecosystems, as vital natural resources, are increasingly endangered by wildfires. Effective forest fire management relies on the accurate and early detection of small–scale flames and smoke. However, the complex and dynamic forest environment, along with the small size and irregular shape of early fire indicators, poses significant challenges to reliable early warning systems. To address these issues, this paper introduces SER–YOLOv8, an enhanced detection model based on the YOLOv8 architecture. The model incorporates the RepNCSPELAN4 module and an SPPELAN structure to strengthen multi-scale feature representation. Furthermore, to improve small target localization, the Normalized Wasserstein Distance (NWD) loss is adopted, providing a more robust similarity measure than traditional IoU–based losses. The newly designed SERDet module deeply integrates a multi–scale feature extraction mechanism with a multi-path fused attention mechanism, significantly enhancing the recognition capability for flame targets under complex backgrounds. Depthwise separable convolution (DWConv) is utilized to reduce parameters and boost inference efficiency. Experiments on the M4SFWD dataset show that the proposed method improves mAP50 by 1.2% for flames and 2.4% for smoke, with a 1.5% overall gain in mAP50–95 over the baseline YOLOv8, outperforming existing mainstream models and offering a reliable solution for forest fire prevention
Learning to Engineer: Integrating Robotics-Centred Project-Based Learning in Early Undergraduate Education
No full textEngineering programmes have been giving more weight to experiential learning, largely because many students still find it difficult to see how classroom theory connects to the work that engineers handle on the ground. With this in mind, a robotics-centred Project-based Learning (PBL) module was introduced to first-year general engineering students as part of the faculty’s engineering spine. The module asks students to design, build, and program small autonomous robots capable of navigating and competing in a set arena. Even a simple task of this kind draws together multiple strands of engineering. Students shift between sketching mechanical layouts, wiring basic circuits, writing code, testing prototypes, and negotiating the usual challenges that arise when several people share responsibility for the same piece of hardware. To explore how students learned through the module, a mixed-methods evaluation was carried out using survey responses alongside reflective pieces written by the students themselves. Certain patterns appeared repeatedly. Many students felt that their technical skills had grown, particularly in breaking down a messy problem into smaller, more workable components. Teamwork also surfaced as a prominent theme. Groups often had to sort out issues such as a robot veering off course due to a misaligned sensor or a block of code producing unpredictable behaviour. These issues were undoubtedly challenging for the students, but they also had a certain pedagogical flavour, with many students describing them as a source of frustration as well as a learning opportunity. Later iterations of the module may benefit from more targeted support at key stages. Despite the many challenges, robotics has been shown to be an attractive way for students to step into engineering practice. The project helped them build technical capability, but it also encouraged habits that matter just as much in real work, such as planning, communicating clearly, and returning to a problem until it behaves as expected. Taken together, the experience offers useful guidance for curriculum designers seeking to create early learning environments that feel authentic and manageable and for motivating students who are just beginning their engineering journey
Isolation of Madariaga Virus (MADV) in a Horse Coinfected with Equine Infectious Anemia in Venezuela: A Review of MADV Circulation in the Country
No full textBackground: Madariaga virus (MADV), formerly known as the South American variant of Eastern Equine Encephalitis virus (EEEV), is an alphavirus that belongs to the Togaviridae family and has been periodically infecting equids in Venezuela since its first identification in 1975. This study reports the isolation and molecular characterization of MADV isolated from a horse in December 2024 in the context of MADV cases reported in Venezuela. Methods: Antibodies to the rabies virus were detected by indirect immunofluorescence, and to the Equine Infectious Anemia virus (EIAV) by passive immunodiffusion. MADV RNA was detected by qRT-PCR. The sequence of the complete viral genome was obtained by next-generation sequencing. Results: The sequence of this virus was highly similar to that of the only human case of MADV reported in the country in 2016, as well as to a sequence of a virus isolated from a horse in Colombia in 2002. The horse was found to be co-infected with EIAV. Conclusions: The continuous circulation of MADV in Venezuela warrants reinforcing the preventive measures against these alphaviruses, which ignore borders, and may cause important animal and human health concerns
Advanced Biomaterial-Based In Vitro Osteoarthritis Models: Integrating Sex as a Biological Variable in Hormonal, Subchondral Bone, and Mechanobiological Pathways
No full textOsteoarthritis (OA) is the most common form of arthritis and represents a major clinical and socioeconomic burden. Epidemiological data consistently show that OA affects women more frequently and, in several joints, more severely than men. Nevertheless, current in vitro models rarely consider sex-specific variables, limiting their ability to capture the biological mechanisms that shape the pathogenesis and progression of OA. Increasing evidence indicates that age-related hormonal fluctuations and subchondral bone remodeling strongly influence OA evolution, and that these processes differ between the sexes. For instance, the decline in estrogen levels during menopause has been associated with accelerated cartilage degeneration, increased osteoclastic activity, and a higher susceptibility to subchondral bone alterations, which may contribute to more aggressive clinical manifestations in women. These mechanisms are only partially reproduced in widely used experimental systems, including traditional biomaterial scaffolds and simplified osteochondral constructs, leaving important sex-dependent pathways unresolved. While advanced biomaterials enable precise control of stiffness, porosity, and biochemical cues, most current in vitro OA models still rely on sex-neutral design assumptions, limiting their ability to reproduce the divergent disease trajectories observed in men and women. By integrating material properties with dynamic loading and tunable hormonal conditions, next-generation in vitro systems could improve mechanistic understanding, increase the reliability of drug screening, and better support the development of sex-specific therapies through the combined efforts of bioengineering, materials science, cell biology, and translational medicine
Discovery of RUVBL1 as a Target of the Marine Alkaloid Caulerpin via MS-Based Functional Proteomics
No full textMarine flora is a significant source of bioactive metabolites. These compounds have been demonstrated to have outstanding bioactivity and biocompatibility, enabling their use in various therapeutic applications. Therefore, examining the biological potential of marine natural compounds remains important, with particular emphasis on their interaction profiles to identify the macromolecular partners they can modulate. This study focused on the interactome profiling of the marine alkaloid caulerpin (CAU), isolated from the alga Caulerpa cylindracea. Along with the discovery of its antitumor properties, this metabolite has garnered attention for its potential therapeutic applications, including modulation of MAO-B and PPARs involved in inflammatory responses, as well as the discovery of its antitumor properties. Two complementary MS-based proteomic approaches were used to identify CAU target proteins in cancer cells: DARTS, which enabled proteome-wide screening to identify proteins interacting with the compound, and t-LIP-MRM-MS, which pinpointed the target protein regions involved in ligand binding. RUVB-like 1 (RUVBL1), a protein that regulates the essential mechanism of carcinogenesis, including chromatin remodeling, DNA repair, and transcriptional control, was discovered as an intriguing CAU target. These results were corroborated via in silico and biological investigations that elucidated CAU role in the regulation of RUVBL1 activity, highlighting its promising therapeutic relevance
A Retrospective Observational Study of Pulmonary Impairments in Long COVID Patients
No full textBackground/Objective: Pulmonary impairments have been identified as some of the most complex and debilitating post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID. This study identified and characterised the specific forms of pulmonary impairments detected using pulmonary function tests (PFT), chest X-rays (CXR), and computed tomography (CT) scans in patients with long COVID symptoms. Methods: We conducted a single-centre retrospective study to evaluate 60 patients with long COVID who underwent PFT, CXR, and CT scans. Pulmonary function in long COVID patients was assessed using defined thresholds for key test parameters, enabling categorisation into normal, restrictive, obstructive, and mixed lung-function patterns. We applied exact binomial (Clopper–Pearson) 95% confidence intervals to calculate the proportions of patients falling below the defined thresholds. We also assessed the relationships among spirometric indices, lung volumes, and diffusion capacity (DLCO) using scatter plots and corresponding linear regressions. The findings from the CXRs and CT scans were categorised, and their prevalence was calculated. Results: A total of 60 patients with long COVID symptoms (mean age 60 ± 13 years; 57% female) were evaluated. The cohort was ethnically diverse and predominantly non-smokers, with a mean BMI of 32.4 ± 6.3 kg/m2. PFT revealed that most patients had preserved spirometry, with mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) above 90% predicted. However, a significant proportion exhibited reductions in lung volumes, with total lung capacity (TLC) decreasing in 35%, and diffusion capacity (DLCO/TLCO) decreasing in 75%. Lung function pattern analysis showed 88% of patients had normal function, while 12% displayed a restrictive pattern; no obstructive or mixed patterns were observed. Radiographic assessment revealed that 58% of chest X-rays were normal, whereas CT scans showed ground-glass opacities (GGO) in 65% of patients and fibrotic changes in 55%, along with findings such as atelectasis, air trapping, and bronchial wall thickening. Conclusions: Spirometry alone is insufficient to detect impairment of gas exchange or underlying histopathological changes in patients with long COVID. Our findings show that, despite normal spirometry results, many patients exhibit significant diffusion impairment, fibrotic alterations, and ground-glass opacities, indicating persistent lung and microvascular damage. These results underscore the importance of comprehensive assessment using multiple diagnostic tools to identify and manage chronic pulmonary dysfunction in long COVID
Crotoxin B from the South American Rattlesnake Crotalus vegrandis Blocks Voltage-Gated Calcium Channels Independent of Its Intrinsic Catalytic Activity
No full textNeurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (CaV) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a non-covalent heterodimer formed by an acidic subunit (CA) and a basic toxic phospholipase A2 subunit (CB). Here, we chromatographically isolated the CB subunit from Crotalus vegrandis and studied its effect on CaV heterologously expressed in tsA201 cells using the whole-cell patch-clamp technique. Mass spectrometry analysis identified a protein that matched with 97% sequence coverage the CBc isoform from Crotalus durissus terrificus. Isolated CB exhibited moderate phospholipase activity that was not correlated to its cytotoxic effect on cultured tsA201 cells. Using Ba2+ as a charge carrier to prevent the enzymatic activity, we found that CB inhibited currents mediated by the N-type CaV2.2 and CaV1.2 L-type calcium channels, in a dose–dependent manner, with higher potency for the latter, and negligible changes in the voltage dependence of channel activation. Our results reveal a novel phospholipase-independent biological activity and a molecular target of CB providing new insights into the pathophysiology of Crotalus snakebite envenoming with potential clinical therapeutic implications