Search Results (1,733)

Two-pore-domain K⁺ channels (K2p), known previously as leak channels, are responsible for maintaining the resting membrane potential of cells. Fifteen subtypes are known to exist in humans and eleven are known in Drosophila melanogaster, as well as six subfamilies; however, little is known about the expression of these subtypes in various animal tissues or the impact of altered expression on cellular physiology. The Drosophila melanogaster model allows for selective misexpression of certain neuron subsets, providing insight into individual cell types and the animal’s physiology more generally. Prior research on the overexpression of K2p channels and the resulting behavioral and neuronal effects is limited. This project expanded upon this prior research by using Drosophila motor neurons to examine the effects of K2p overexpression on behavior and physiology. After conducting various assays, it was concluded that K2p overexpression in motor neurons had the most prominent effects on Drosophila functioning, with sensory, cardiac, and chordotonal neurons also generating differences in behavior. Altered expression levels of K2p channels could result in tissue-specific and/or whole-animal dysfunction. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant widely used in consumer products. TBBPA is often detected in soil, water, organisms, and even in human blood and breast milk. Hence, it is accessible to developing fetuses and nursing offspring after maternal exposure. The reported evidence for the endocrine disruption of TBBPA in the brain has raised concerns regarding its effects on neurodevelopmental and behavioral functions. This study investigated the effects of TBBPA exposure on neurodevelopment. A cell-based developmental neurotoxicity assay was performed to determine whether TBBPA is a developmental neurotoxicant. The assay revealed TBBPA to be a developmental neurotoxicant. C57BL/6N maternal mice were administered TBBPA at 0, 0.24, and 2.4 mg/kg during pregnancy and lactation, and their offspring underwent behavioral testing. The behavioral experiments revealed sex-specific effects. In females, only a deterioration of the motor ability was observed. In contrast, deteriorations in motor function, memory, and social interaction were noted in males. Furthermore, we validated changes in the expression of genes associated with behavioral abnormalities, confirming that perinatal exposure to TBBPA, at the administered doses, can affect neurodevelopment and behavior in offspring. These findings highlight the need for more in-depth and multifaceted research on the toxicity of TBBPA. Full article

Background and Clinical Significance: Myxoid liposarcoma (MLS) is a malignant soft tissue tumor that often presents as a painless, slow-growing mass and is known for its atypical extrapulmonary metastatic pattern. Although sciatic nerve involvement is rare, when present, it usually causes neurologic symptoms. In this case, a large MLS silently expanded and completely encased the sciatic nerve without causing deficits, highlighting the importance of early imaging, multidisciplinary planning, and individualized surgical strategy in managing complex soft tissue sarcomas. Case Presentation: This case report describes a 67-year-old male with a 30 cm encapsulated myxoid liposarcoma of the posterior left thigh. The tumor had grown insidiously over one year and completely encased the sciatic nerve without causing pain, paresthesia, or motor impairment. Selective embolization was performed preoperatively to minimize blood loss. A posteromedial surgical approach allowed for en bloc resection with negative margins and preservation of sciatic nerve integrity. Histopathology confirmed a myxoid liposarcoma composed primarily of spindle-shaped tumor cells. The patient experienced no postoperative complications or neurologic deficits. At the two-year follow-up, he remains disease-free with full functional recovery. Conclusions: This case illustrates the potential for large, asymptomatic myxoid liposarcomas to encase critical neurovascular structures without infiltration. Preoperative embolization as part of a multidisciplinary plan was key to achieving safe resection and excellent functional outcomes. Full article

Digital Twins (DTs) are transforming manufacturing by bridging the physical and digital worlds, enabling real-time insights, predictive analytics, and enhanced decision making. In Industry 4.0, DTs facilitate automation and data integration, while Industry 5.0 emphasizes human-centric, resilient, and sustainable production. However, implementing DTs in robotic metal additive manufacturing (AM) remains challenging because of the complexity of the wire-based laser metal deposition (LMD) process, the need for real-time monitoring, and the demand for advanced defect detection to ensure high-quality prints. This work proposes a structured DT architecture for a robotic wire-based LMD cell, following a standard framework. Three DT implementations were developed. First, a real-time 3D simulation in RoboDK, integrated with a 2D Node-RED dashboard, enabled motion validation and live process monitoring via MQTT (message queuing telemetry transport) telemetry, minimizing toolpath errors and collisions. Second, an Industrial IoT-based system using KUKA iiQoT (Industrial Internet of Things Quality of Things) facilitated predictive maintenance by analyzing motor loads, joint temperatures, and energy consumption, allowing early anomaly detection and reducing unplanned downtime. Third, the Meltio dashboard provided real-time insights into the laser temperature, wire tension, and deposition accuracy, ensuring adaptive control based on live telemetry. Additionally, a prescriptive analytics layer leveraging historical data in FireStore was integrated to optimize the process performance, enabling data-driven decision making. Full article

Spinal muscular atrophy (SMA) is a fatal motor neuron disease characterized by five clinical subtypes, each presenting with different rates of disease progression and varying responses to recently approved therapies. The identification of reliable biomarkers is essential for improving diagnosis and prognosis, monitoring disease progression, enabling personalized treatment strategies, and evaluating therapeutic responses. In this review, we conducted a comprehensive literature search using PubMed and Web of Science with the keywords “spinal muscular atrophy”, “biomarker” and advanced technologies such as “single-cell omics”, “nanopore and long-read sequencing” and “epigenetics” to identify and summarize current advances in SMA biomarker discovery and application. We begin with a brief overview of SMA and its current treatment barriers. We then conclude with well-established and emerging molecular and non-molecular biomarkers, followed by a conclusion of emerging technologies in biomarker discovery. In the meantime, we highlight the application of biomarkers in key areas, including early diagnosis and disease stratification, monitoring of disease progression, and prediction of treatment response. Finally, we summarize biomarker-targeted therapies, addressing current challenges in biomarker research, with the goal of improving clinical outcomes for patients with SMA. Full article

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that affects motor neurons of people, leading to death. This pathology can be caused by mutations in different genes, including superoxide dismutase 1 (SOD1). Previous studies have pointed out the presence of two transcripts of SOD1, a short one and a long one. The aim of this study was the investigation of these two transcripts both in the SH-SY5Y cell line and in patients’ peripheral blood mononuclear cells. We found that the shortest SOD1 transcript is upregulated under stress conditions in both the cellular model and the patients’ cells. Moreover, we found a potential correlation between the short SOD1 transcript and the severity of the pathology, which also correlates with the age of patients. No correlation was found between SOD1 transcripts and the progression of the disease. These data suggest a toxic effect of short SOD1 transcripts in ALS patients, by affecting the severity of the pathology making it a possible biomarker for this disease. Interestingly, our data suggest that a short SOD1 transcript does not influence and drive disease progression. The finding of a biomarker will have suitable implications as indicators of disease severity and from the perspective of drug development. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It primarily affects the motor system but is also associated with a range of cognitive impairments that can manifest early in disease progression, indicating its multifaceted nature. In this paper, we performed a meta-analysis of transcriptomics and proteomics data using MultiOmicsIntegrator to gain insights into the post-transcriptional modifications and deregulated pathways associated with this disease. Our results reveal differential isoform usage between control and PD patient brain samples that result in enriched alternative splicing events, including an extended UTR length, domain loss, and the upregulation of non-coding isoforms. We found that Inositol-Requiring Enzyme 1 (IRE1) is active in PD samples and examined the role of its downstream signaling through X-box binding mRNA 1 (XBP1) and regulated IRE1-dependent decay (RIDD). We identified several RIDD candidates and showed that the enriched alternative splicing events observed are associated with RIDD. Moreover, in vitro mRNA cleavage assays demonstrated that OSBPL3, C16orf74, and SLC6A1 mRNAs are targets of IRE1 RNAse activity. Finally, a pathway enrichment analysis of both XBP1s and RIDD targets in the PD samples uncovered associations with processes such as immune response, oxidative stress, signal transduction, and cell–cell communication that have previously been linked to PD. These findings highlight a potential regulatory role of IRE in PD. Full article

Spinal cord injury (SCI) is a severe neurological condition that typically results in irreversible loss of motor and sensory function. Emerging evidence indicates that neuroplasticity, the ability of the nervous system to reorganize by forming new neural connections, plays a pivotal role in structural and functional recovery post-injury. This insight lays the groundwork for the development of rehabilitation and therapeutic strategies designed to leverage neuroplasticity. In this review, we offer an exhaustive overview of the neuroplastic alterations and mechanisms that occur following an SCI. We examine the role of neuroplasticity in functional recovery and outline therapeutic approaches designed to augment neuroplasticity post-SCI. The process of neuroplasticity post-SCI involves several physiological processes, such as neurogenesis, synaptic remodeling, dendritic spine formation, and axonal sprouting. Together, these processes contribute to the reestablishment of neural circuits and functional restoration. Enhancing neuroplasticity is a promising strategy for improving functional outcomes post-SCI; however, its effectiveness is influenced by numerous factors, including age, injury severity, time since the injury, and the specific therapeutic interventions employed. A variety of strategies have been suggested to promote neuroplasticity and expedite recovery, including pharmacological treatments, biomaterial-based therapies, gene editing, stem cell transplantation, and rehabilitative training. The combination of personalized rehabilitation programs with innovative therapeutic techniques holds considerable potential for maximizing the benefits of neuroplasticity and enhancing clinical outcomes in SCI management. Full article

Amyotrophic lateral sclerosis (ALS) is a progressive disease that degeneratively damages both upper and lower motor neurons, eventually resulting in muscular paralysis and death. Although ALS is broad in scope and commonly thought of as a motor neuron disease, more active research sheds light on the that role skeletal muscle plays in the development and progression of the disease. Muscle tissue in ALS patients and in animal models demonstrates severe regenerative deficits, including impaired myogenesis and impaired myoblast fusion. In ALS, muscle stem cells, known as satellite cells, show poor performance in activation, proliferation, and differentiation and thus contribute to ALS muscle wasting. Moreover, the pathological tissue environment that inhibits myoblast fusion is made up of proinflammatory cytokines, oxidative stress, and a lack of trophic signals from the neuromuscular junction, which greatly disrupts homeostatic regulation. It is likely that skeletal muscle is instead a dynamic player, fueling neuromuscular degeneration as opposed to a passive responder to denervation. One must appreciate the cellular and molecular changes that complicate muscle regeneration in ALS for effective treatment to be developed, permitting simultaneous interventions with both muscle and neurons. Full article

Schwann cells (SCs) play a crucial role in peripheral nerve repair by supporting axonal regeneration and remyelination. While extensive research has been conducted using rodent SCs, increasing attention is being directed toward human SCs due to species-specific differences in phenotypical and functional properties, and accessibility of human SCs derived from diverse sources. A major challenge in translating SC-based therapies for nerve repair lies in the inability to replicate human SC myelination in vitro, posing a significant obstacle to drug discovery and preclinical research. In this study, we compared the myelination capacity of human, rodent, and porcine SCs in various co-culture conditions, including species-matched and cross-species neuronal environments in a serum-free medium. Our results confirmed that rodent and porcine SCs readily myelinate neurites under standard culture conditions after treatment with ascorbic acid for two weeks, whereas human SCs, at least within the four-week observation period, failed to show myelin staining in all co-cultures. Furthermore, we investigated whether cell culture manipulation impairs human SC myelination by transplanting freshly harvested and predegenerated human nerve segments into NOD-SCID mice for four weeks. Despite supporting host axonal regeneration into the grafts, human SCs exhibited very limited myelination, suggesting an intrinsic species-specific restriction rather than a cell culture-induced defect. These observations suggest fundamental differences between human and rodent SCs and highlight the need for human-specific models and protocols to advance our understanding of SC myelination. Full article

Due to the high demand for fuel efficiency, electric vehicles have come into the picture, as they only use batteries to power the vehicle. This requires constant charging of the batteries at charging stations, which are costly and impractical to install. But it is possible to install charging stations by making use of photovoltaic (PV) cells and demagnetization currents to self-charge batteries under stand-still conditions. The design of a bidirectional converter with asymmetrical half-bridge converter based on a switched reluctance motor (SRM) drive, using PV for electric vehicles, is implemented in this paper. It consists of developing a control unit (GCU), Li-ion battery pack, and photovoltaic (PV) solar cells that are integrated with a bidirectional converter and asymmetrical half-bridge converter (AHBC) to provide power to the SRM drive. The solar-assisted SRM drive can be operated in either the motoring mode or charging mode. In the motoring-mode GCU, the battery or PV energy can be used in any combination to power the SRM. In the charging-mode PV, the GCU and AC grids are used to charge the battery under stand-still conditions. This work helps in the self-charging of batteries using either the GCU or PV cells, as well as aids in the improvement in the performance characteristics. Also, this work compares the performance metrics for the proposed system and conventional system. The performance of the drive system using PV cells/GCU is evaluated and verified through MatLab/Simulink and experimental results. Full article

Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs? Methods: Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined. Results: The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints. Conclusions: We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective. Full article

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by ¹H-MR spectroscopy. Full article