Search Results (23,569)

Fabry disease (FD) is a lysosomal disorder due to alpha-galactosidase-A enzyme deficiency, accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) which lead to proinflammatory effects. Males develop progressive hypertrophic cardiomyopathy (HCM) followed by fibrosis; females develop nonconcentric hypertrophy and/or early fibrosis. The inflammatory response to Gb3/lyso-Gb-3 accumulation is one of the suggested pathogenic mechanisms in FD cardiomyopathy when the secretion of inflammatory and transforming growth factors with infiltration of lymphocytes and macrophages into tissue promotes cardiofibrosis. This study aims to evaluate inflammation-driving cytokines and cardio-hypertrophic remodeling biomarkers contributing to sex-specific HCM progression. Biomarkers were studied in 20 healthy subjects and 45 FD patients. IL-2, IL-10, TNF-α, and IFN-γ were elevated in all patients, while IL-1α, MCP-1, and TNFR2 showed sex-specific differences. The increased cytokines were associated with the NF-kB pathway in FD males with HCM, revealing a correlation between MCP-1, IFN-γ, VEGF, GM-CSF, IL-10, and IL-2. In female patients, the impaired TNFα/TNFR2/TGFβ cluster with correlations to MCP-1, VEGF, GM-CSF, and IL-1α was observed. The activation of cytokines and the NF-kB pathway indicates significant inflammation during HCM remodeling in FD males. The TNFα/TNFR2/TGFβ signaling cluster may explain early fibrosis in females with FD cardiomyopathy. Sex-specific inflammatory responses in FD influence the severity and progression of HCM. Full article

The Apetala2/Ethylene Responsive Factor (AP2/ERF) family represents a critical group of transcription factors in plants, recognized for their roles in growth, development, fruit ripening, and postharvest processes. This study aimed to identify and characterize the AP2/ERF gene family in passion fruit (Passiflora edulis Sims) and investigate their potential roles in flavor enhancement. A total of 91 PeAP2/ERF genes were identified and classified into five subfamilies. Chromosome localization and collinearity analysis demonstrated their distribution across all nine chromosomes of passion fruit, with tandem duplication events identified as a key driver of family expansion. Exon–intron configurations and motif compositions were highly conserved among PeAP2/ERF genes. Promoter cis-acting element analysis indicated potential regulation by environmental signals, including abiotic and biotic stresses, as well as hormonal cues. Postharvest storage induced the expression of 59 PeAP2/ERF genes over time. Notably, PeAP2-10 was found to enhance the expression of PeSTP6, a gene associated with sugar transport, suggesting its potential influence on the flavor profile of passion fruit. These findings provide valuable insights into the functional roles of PeAP2/ERF genes in passion fruit, highlighting their significance in postharvest management and flavor quality enhancement strategies. Full article

Experimental evidence suggests that alkaloids have anti-influenza and anti-inflammatory effects. However, the risk of translating existing evidence into clinical practice is relatively high. We conducted a systematic review and meta-analysis of animal studies to evaluate the therapeutic effects of alkaloids in treating influenza, providing valuable references for future studies. Seven electronic databases were searched until October 2024 for relevant studies. The Review Manager 5.2 software was utilized to perform the meta-analysis. Our study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42024607535. Alkaloids are significantly correlated with viral titers, pulmonary inflammation scores, survival rates, lung indices, and body weight. However, alkaloid therapy is not effective in reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, the therapeutic effects of alkaloids may be related to the inhibition of the Toll-like receptor 4 or 7/Nuclear factor (NF)-κB signaling pathway, NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome pathway, and the Antiviral innate immune response receptor RIG-I (RIG-I) pathway. Alkaloids are potential candidates for the prevention and treatment of influenza. However, extensive preclinical studies and clinical studies are needed to confirm the anti-influenza and anti-inflammatory properties of alkaloids. Full article

Background/Objectives: This systematic review presents how neural and emotional networks are integrated into EEG-based emotion recognition, bridging the gap between cognitive neuroscience and practical applications. Methods: Following PRISMA, 64 studies were reviewed that outlined the latest feature extraction and classification developments using deep learning models such as CNNs and RNNs. Results: Indeed, the findings showed that the multimodal approaches were practical, especially the combinations involving EEG with physiological signals, thus improving the accuracy of classification, even surpassing 90% in some studies. Key signal processing techniques used during this process include spectral features, connectivity analysis, and frontal asymmetry detection, which helped enhance the performance of recognition. Despite these advances, challenges remain more significant in real-time EEG processing, where a trade-off between accuracy and computational efficiency limits practical implementation. High computational cost is prohibitive to the use of deep learning models in real-world applications, therefore indicating a need for the development and application of optimization techniques. Aside from this, the significant obstacles are inconsistency in labeling emotions, variation in experimental protocols, and the use of non-standardized datasets regarding the generalizability of EEG-based emotion recognition systems. Discussion: These challenges include developing adaptive, real-time processing algorithms, integrating EEG with other inputs like facial expressions and physiological sensors, and a need for standardized protocols for emotion elicitation and classification. Further, related ethical issues with respect to privacy, data security, and machine learning model biases need to be much more proclaimed to responsibly apply research on emotions to areas such as healthcare, human–computer interaction, and marketing. Conclusions: This review provides critical insight into and suggestions for further development in the field of EEG-based emotion recognition toward more robust, scalable, and ethical applications by consolidating current methodologies and identifying their key limitations. Full article

Cryptosporidium, a protozoan parasite affecting the gastrointestinal system, is primarily known for causing diarrhea, especially in those with weakened immune systems. However, there is increasingly persuasive evidence that it may be directly involved in tumorigenesis. This review examines some of the potential mechanisms through which Cryptosporidium infections can induce cancer, specifically chronic inflammation, manipulation of the immune system, and alteration of cell signaling pathways. Persistent inflammation with immune system changes due to chronic infection, particularly among immunocompromised hosts, leads to a microenvironment that facilitates tumorigenesis. Cryptosporidium manipulates important cellular pathways such as PI3K, NF-κB, Wnt, and p38/MAPK to promote cell survival, regulate immune responses, and foster tissue remodeling, all of which contribute to a tumor-friendly microenvironment. Moreover, Cryptosporidium virulence factors such as ROP1, sPLA2, and microRNAs disrupt host cellular stability and significantly alter host cellular gene expression, which also exacerbates inflammation and tissue damage. Epidemiological data have indicated higher rates of Cryptosporidium infection in cancer patients, especially patients with gastrointestinal cancers. This, among other observations, raises the possibility that the infection may be connected to cancer progression. In animal models, especially studies with C. parvum-challenged rodents, chronic inflammation, immune repression, and genetic mutations related to neoplasia have been reported. While this has provided us with valuable information, we still have a long way to go to fully understand the long-term ramifications of Cryptosporidium infection. These cover aspects such as the contribution of latent infections and the genetic diversity of Cryptosporidium strains in cancer. Further investigation is urgently needed to understand the molecular processes by which Cryptosporidium might contribute to carcinogenesis and explore potential strategies for therapy and prevention especially among immunocompromised populations. Full article

Gracilaria species, a widely distributed genus of red macroalgae, have gathered significant attention for their diverse medical applications attributable to their bioactive sulphated polysaccharides (SPs). This review examines the global narrative of various Gracilaria SP applications in terms of their therapeutic potential and mechanistic insights into the use of these SPs against a range of medical conditions, including cancer, inflammation, neurodegenerative disorders, diabetes, and immune dysfunctions. SPs extracted from G. lemaneiformis and G. fisheri have demonstrated potent anti-tumour activities by inducing apoptosis through various mechanisms, including the upregulation of CD8⁺ T cells and IL-2, inhibition of EGFR/MAPK/ERK signalling pathways, and activation of the Fas/FasL pathway. Selenium nanoparticles (SeNPs) conjugated with SPs further enhanced the targeted delivery and efficacy of these SPs against glioblastoma by the downregulation of ROS followed by the activation of p53, MAPK, and AKT pathways. The anti-inflammatory properties of SPs are evidenced by key suppressive inflammatory markers like NO, TNF-α, IL-1β, and IL-6 in mutant rodent models. SPs from G. cornea and G. birdiae effectively reduce neutrophil migration and vascular permeability, offering potential treatments for acute inflammation and conditions such as colitis by modulating pathways involving COX-2 and NF-κB. Neuroprotective effects by SPs (from G. cornea and G. gracili) studied in 6-OHDA-induced rats, which mitigate oxidative stress and enhance neuronal cell viability, facilitate the management of neurodegenerative diseases like Parkinson’s and Alzheimer’s. Regarding the hypoglycaemic effect, SPs from G. lemaneiformis exhibit a glucose-modulating response by improving insulin regulation, inhibiting α-amylase activity, repairing pancreatic β-cells, and modulating lipid metabolism. Moreover, immunomodulatory activities of Gracilaria-derived SPs include the stimulation of macrophages, T-cell proliferation, and cytokine production, underscoring their potential as functional food and immunotherapeutic agents. Recently, Gracilaria-derived SPs have been found to modulate gut microbiota, promote SCFA production, and enhance gut microbials, suggesting their potential as prebiotic agents (G. rubra and G. lemaneiformis). This review highlights the multifaceted medical applications of Gracilaria sulphated polysaccharides, providing detailed mechanistic insights and suggesting avenues for future clinical translation and therapeutic innovations. Full article

Increasing evidence shows that a very small population of cancer stem cells (CSCs) is responsible for cancer recurrence, drug resistance, and metastasis. CSCs usually reside in hypoxic tumor regions and are characterized by high tumorigenicity. Their inaccessible nature allows them to avoid the effects of conventional treatments such as chemotherapy, radiotherapy, and surgery. In addition, conventional chemo- and radiotherapy is potentially toxic and could help CSCs to spread and survive. New therapeutic targets against CSCs are sought, including different signaling pathways and distinct cell surface markers. Recent advances in nanotechnology have provided hope for the development of new therapeutic avenues to eradicate CSCs. In this review, we present newly discovered nanoparticles that can be co-loaded with an apoptosis-inducing agent or differentiation-inducing agent, with high stability, cellular penetration, and drug release. We also summarize the molecular characteristics of CSCs and the signaling pathways responsible for their survival and maintenance. Controlled drug release targeting CSCs aims to reduce stemness-related drug resistance, suppress tumor growth, and prevent tumor relapse and metastases. Full article

In ruminants, the survival and development of the conceptus are heavily dependent on the composition of the uterine lumen fluid (ULF), which is influenced by prostaglandins (PGs). However, the variations in underlying PG-mediated ULF remain unclear. Herein, cycling heifers received an intrauterine infusion of vehicle as a control (CON) or meloxicam (MEL) on days 12–14 of the estrous cycle. Then, the ULF was collected on day 15 and alternations in its protein and lipid levels were analyzed. The suppression of prostaglandins induced by meloxicam resulted in 1343 differentially abundant proteins (DAPs) and 59 differentially altered lipids. These DAPs were primarily associated with vesicle-mediated transport, immune response, and actin filament organization, and were mainly concentrated on the ribosome, complement and coagulation cascades, cholesterol metabolism, chemokine signal pathway, regulation of actin cytoskeleton and starch and sucrose metabolism. These differential lipids reflected a physiological metabolic shift as the abundance of cell membrane-related lipids was modulated, including an accumulation of triacylglycerols and reductions in lysophosphatidylcholines, hexosyl ceramides, ceramides, and sphingomyelins species. Integration analysis of the DAPs and differentially altered lipid metabolites revealed that glycerophospholipid metabolism and choline metabolism were the core pathways. These findings highlight the potential roles of prostaglandins in ULF, providing new insights into the contributions of prostaglandins in the development of the conceptus. Full article

Compared to the negative effect of directional selection on genetic diversity, balancing selection acts oppositely and maintains variability across the genome. This study aims to articulate whether balancing selection leads to heterozygosity-rich region islands (HRRIs) forming in the canine genome by investigating 1000 animals belonging to 50 dog breeds via 153,733 autosomal SNPs. A consecutive SNP-based approach was used to identify heterozygosity-rich regions (HRRs). Signals of balancing selection in the genome of studied breeds were then assessed with Tajima’s D statistics. A total of 72,062 HRRs with an average length of 324 kb were detected to be unevenly distributed across the genome. A total of 509 and 450 genomic regions were classified as HRRIs and balancing selection signals, respectively. Although the genome-wide distributions of HRRIs varied across breeds, several HRRIs were found in the same locations across multiple breeds. A total of 109 genomic regions were classified as both HRRIs and signals of balancing selection. Even though the genomic coordinates of HRRIs and balancing selection signals did not fully overlap across all genomic regions, balancing selection may play a significant role in maintaining diversity in regions associated with various cancer diseases, immune response, and bone, skin, and cartilage tissue development. Full article

Perfluorooctane sulfonate (PFOS) contamination poses a significant environmental threat due to its widespread distribution and persistence. However, the hepatotoxic effects of PFOS on key aquatic species, such as crucian carp, remain understudied. This study systematically investigated the hepatotoxicity and underlying molecular mechanisms associated with PFOS exposure in crucian carp over a 21 day period. We determined a 96 h 50% lethal concentration (LC₅₀) of 23.17 mg/L. Histopathological and transcriptomic analyses confirmed PFOS-induced liver damage in the carp, characterized by venous congestion, nucleolar dissolution and cellular vacuolation. Transcriptomic profiling further identified 1036 differentially expressed genes (DEGs), involving critical pathways related to lipid and energy metabolism, immunity, and endocrine regulation. These pathways are integral to the development of nonalcoholic fatty liver disease (NAFLD). Specifically, DEGs related to lipid metabolism showed significant changes, while those involved in energy metabolism indicated disrupted ATP production and mitochondrial function. Genes associated with immune response revealed an upregulation of pro-inflammatory markers, and hormone regulation genes highlighted alterations in endocrine signaling. Our findings emphasized that PFOS exhibits acute toxicity to crucian carp, potentially inducing hepatotoxicity by disrupting multiple physiological systems. This research provides a theoretical foundation for mitigating aquatic pollution and protecting eco-health, contributing to broader ecological and conservation biology discussions. Full article

SHEDs have demonstrated significant potential in cell therapy due to their superior proliferation rate, self-renewal and differentiation capacity (particularly neurogenesis attributed to their neural crest origin), and the less invasive procedure required for tissue collection compared to other stem cells. However, there is no established criterion to verify the minimum qualification to select one from numerous candidates, especially for SHEDs’ cultured FBS-free medium for clinic application. For that, we performed a characteristic analysis containing the growth rate, colony-forming unit (CFU) number, average colony size, and migration capacity with hPL-cultured SHEDs from 21 different donors, and we suggest the result as a minimum standard to filter out unqualified candidates. In addition, in the secretome analysis to predict the paracrine effect, it was found that upregulated proteins compared to the control were related to angiogenesis, immune response, and BMP signaling, and this was found to have a strong correlation only with protein concentration. This study presents a minimum standard for selecting cell therapy candidates and suggests the protein concentration of a conditioned medium as a cost-effective tool to expect the paracrine effect of SHEDs. Full article

Plants are constantly exposed to abiotic and biotic stresses that seriously affect crop yield and quality. A coordinated regulation of plant responses to combined abiotic/biotic stresses requires crosstalk between signaling pathways initiated by each stressor. Interconnected signaling pathways further finetune plant stress responses and allow the plant to respond to such stresses effectively. The plant nutritional status might influence disease resistance by strengthening or weakening plant immune responses, as well as through modulation of the pathogenicity program in the pathogen. Here, we discuss advances in our understanding of interactions between nutrient stress, deficiency or excess, and immune signaling pathways in the context of current agricultural practices. The introduction of chemical fertilizers and pesticides was a major component of the Green Revolution initiated in the 1960s that greatly boosted crop production. However, the massive application of agrochemicals also has adverse consequences on the environment and animal/human health. Therefore, an in-depth understanding of the connections between stress caused by overfertilization (or low bioavailability of nutrients) and immune responses is a timely and novel field of research with important implications for disease control in crop species. Optimizing nutrient management practices tailored to specific environmental conditions will be crucial in maximizing crop production using environmentally friendly systems. Full article

Background: Retinopathy of prematurity (ROP) is the major cause of blindness in children. It is a biphasic disease with retinal vessel growth cessation and loss (Phase I) followed by uncontrolled retinal vessel growth (Phase II). Folate is an essential nutrient for fetal development and growth. Premature infants have a high risk for folate deficiency. However, the contribution of folate to ROP risk remains unknown. Methods: In mouse oxygen-induced retinopathy (OIR), the nursing dams were fed with a folic acid-deficient or control diet after delivery until the end of hyperoxia. Alternatively, pups received direct injection of either folic acid or vehicle during Phase I hyperoxia. Genes involved in the folate cycle and angiogenic responses were examined using real-time PCR. Total retinal folate levels were measured with the Lactobacillus casei assay. Results: Maternal folic acid deficiency in early life exacerbated pathological retinal vessel growth, while supplementation with folic acid suppressed it. Genes involved in the folate cycle were downregulated in Phase I OIR retinas and were highly expressed in Müller glia. Folic acid reduced pro-angiogenic signaling in cultured rat retinal Müller glia in vitro. Conclusions: Appropriate supplementation of folic acid might be a new and safe treatment for ROP at an early stage. Full article

This paper presents research on active vibration control (A-V-C), which is being carried out to reduce structural vibration in the field of active vibration control and describes the most important method of implementation. Non-adaptive and adaptive systems feedback with adaptive algorithms are outlined. Electrodynamic shakers, used to excite an SDOF system to study its dynamic characteristics, are introduced. Signal analysis determines the response of a system under known excitation and presents it in a convenient form. The proposed method directly measures the payload displacement relative to the ground. We carry out a detailed investigation based on a realistic single-degree-of-freedom (SDOF), demonstrate the effectiveness of the proposed adaptive control law, estimate the control parameters, and show that the target dynamics of the isolator are attained. Full article

Dynamic manipulation of light in optical fibers has attracted extensive interest due to its compatibility with various fiber-optic systems. The integration of two-dimensional (2D) materials on the surface of optical fibers is an effective method to manipulate light beams. However, it is still a huge challenge to acquire dynamic modulation for light signals in fiber. In this work, we develop electrically manipulable in-line multilayer graphene (MLG) devices by integrating a graphene-based lithium-ion (Li-ion) battery on a side-polished fiber. Through charge and discharge processes with a current of 400 µA, the output power of a 1550 nm laser can be cyclically tuned in the range of ~120 and ~240 µW with a response time of about 1.8 min. After 100 cycles of testing, the modulation power of the laser system remains nearly unchanged, exhibiting good stability. The optical modification of MLG is due to the shift of Fermi energy (E_f), which results from charge transfer between Li and graphene layers. Therefore, the light in the fiber can be modulated due to the change in the optical absorbance of MLG. Our findings imply potential value in fabricating fiber-intergraded 2D intercalation materials with high tunability. Full article