Search Results (45)

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

Endothelial dysfunction and chronic inflammation are determining factors in the development and progression of chronic degenerative diseases, such as hypertension and atherosclerosis. Among the shared pathophysiological characteristics of these two diseases is a metabolic disorder of lipids and lipoproteins. Therefore, the contents and quality of the lipids and proteins of lipoproteins become the targets of therapeutic objective. One of the stages of lipoprotein formation occurs through the incorporation of dietary lipids by enterocytes into the chylomicrons. Consequently, the composition, structure, and especially the properties of lipoproteins could be modified through the intake of bioactive compounds. The objective of this review is to describe the roles of the different lipid and protein components of lipoproteins and their receptors in endothelial dysfunction and the development of hypertension. In addition, we review the use of some non-pharmacological treatments that could improve endothelial function and/or prevent endothelial damage. The reviewed information contributes to the understanding of lipoproteins as vehicles of regulatory factors involved in the modulation of inflammatory and hemostatic processes, the attenuation of oxidative stress, and the neutralization of toxins, rather than only cholesterol and phospholipid transporters. For this review, a bibliographic search was carried out in different online metabases. Full article

The global transportation sector is transitioning towards renewable energy to combat climate change, with biodiesel playing a critical role. Significant research over the past decades has focused on enhancing biodiesel through novel feedstocks and production methods. The defense community, a major diesel consumer, is particularly interested in biodiesel to support national sustainability goals while also leveraging the benefits of the new technology, including the ability to produce biodiesel locally at the point of need. This paper sets out to review recent advances in biodiesel technology and aligning them with the needs of the defense communities. By doing so, this paper provides insight into the challenges, benefits, and technical feasibility for the two primary consumers of military diesel fuel—naval ships and ground vehicles. For naval applications, algae-based biodiesel shows promise due to its potential for local production near ports. Advances in genetic engineering and cultivation are crucial for increasing lipid content and reducing costs. Innovative methods such as microwave-assisted transesterification and artificial neural networks for optimization could further enhance economic viability. In military ground vehicles, locally produced biodiesel could sustain operations by minimizing supply chain dependencies. Efforts are ongoing to develop mobile production facilities and improve feedstock diversity and methanol-independent transesterification processes. Overall, advancements in biodiesel production from various feedstocks and innovative techniques are poised to significantly benefit the military sector, promoting sustainability and operational efficiency. Full article

This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles of ECVs. A unique aspect of this review is the emphasis on the circadian-controlled release and composition of exosomes, highlighting their potential as biomarkers for early cancer detection and monitoring metastasis. We also discuss how circadian rhythms affect multiple cancer-related pathways, proposing that disruptions in the circadian clock can alter tumor development and treatment response. Additionally, this review delves into the influence of circadian clock components on ECV biogenesis and their impact on reshaping the tumor microenvironment, a key component driving HCC progression. Finally, we address the potential clinical applications of ECVs, particularly their use as diagnostic tools and drug delivery vehicles, while considering the challenges associated with clinical implementation. Full article

Worldwide meat consumption and production have nearly quintupled in the last 60 years. In this context, research and the application of new technologies related to animal reproduction have evolved in an accelerated way. The objective of the present study was to apply nanoemulsions (NEs) as carriers of lipids to feed bovine embryos in culture media and verify their impact on the development of embryos produced in vitro. The NEs were characterized by particle size, polydispersity, size distribution, physical stability, morphology using atomic force microscopy (AFM), surface tension, density, pH, and rheological behavior. The NEs were prepared by the emulsification/evaporation technique. A central composite rotatable design (CCRD) was used to optimize the NE fabrication parameters. The three optimized formulations used in the embryo application showed an emulsion stability index (ESI) between 0.046 and 0.086, which reflects high stability. The mean droplet diameter analyzed by laser diffraction was approximately 70–80 nm, suggesting a possible transit across the embryonic zona pellucida with pores of an average 90 nm in diameter. AFM images clearly confirm the morphology of spherical droplets with a mean droplet diameter of less than 100 nm. The optimized formulations added during the higher embryonic genome activation phase in bovine embryos enhanced early embryonic development. Full article

Perfluroalkyl substances (PFASs) are persistent man-made chemicals considered to be emerging pollutants, with Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), and Perfluorohexanesulphonic acid (PFHxS) being linked to hepatotoxicity and steatosis. PFOA, PFOS, and PFHxS can undergo placental and lactational transfer, which results in PFOA, PFOS, and PFHxS distribution to the neonatal liver. Moreover, in pregnant dams, exposure to a PFAS mixture, in combination with a high fat diet, increased hepatic steatosis in offspring at postnatal day 21, but the mechanisms have not been elucidated. It was hypothesized that gestational/lactational PFAS exposure would alter the pup liver proteome and biochemical/signaling pathways. Timed-pregnant CD-1 dams were fed a standard chow or 60% kcal high-fat diet. From GD1 until PND20, dams were dosed via oral gavage with vehicle (0.5% Tween 20), individual doses of PFOA, PFOS, PFHxS at 1 mg/kg, or a mixture (1 mg/kg each, totaling 3 mg/kg). Livers were collected from PND21 offspring and SWATH-MS proteomics was performed. IPA analysis revealed PFAS exposure modified disease and biological function pathways involved in liver damage, xenobiotics, and lipid regulation in the PND21 liver. These pathways included lipid and fatty acid transport, storage, oxidation, and synthesis, as well as xenobiotic metabolism and transport, and liver damage and inflammation. This indicates the pup liver proteome is altered via maternal exposure and predisposes the pup to metabolic dysfunctions. Full article

The impact of microplastics (MPs) on the metabolic functions of the liver is currently unclear and not completely understood. To investigate the effects of the administration of MPs on the hepatic metabolism of normal and obese mice, alterations in the lipid, glucose (Glu), and amino acid regulation pathways were analyzed in the liver and adipose tissues of C57BL/6Korl (wild type, WT) or C57BL/6-Lep^em1hwl/Korl mice (leptin knockout, Lep KO) orally administered polystyrene (PS) MPs for 9 weeks. Significant alterations in the lipid accumulation, adipogenesis, lipogenesis, and lipolysis pathways were detected in the liver tissue of MP-treated WT and Lep KO mice compared to the vehicle-treated group. These alterations in their liver tissues were accompanied by an upregulation of the serum lipid profile, as well as alterations in the adipogenesis, lipogenesis, and lipolysis pathways in the adipose tissues of MP-treated WT and Lep KO mice. Specifically, the level of leptin was increased in the adipose tissues of MP-treated WT mice without any change in their food intake. Also, MP-induced disruptions in the glycogenolysis, Glu transporter type 4 (GLUT4)-5′ AMP-activated protein kinase (AMPK) signaling pathway, levels of lipid intermediates, and the insulin resistance of the liver tissues of WT and Lep KO mice were observed. Furthermore, the levels of seven endogenous metabolites were remarkably changed in the serum of WT and Lep KO mice after MP administrations. Finally, the impact of the MP administration observed in both types of mice was further verified in differentiated 3T3-L1 adipocytes and HepG2 cells. Thus, these results suggest that the oral administration of MPs for 9 weeks may be associated with the disruption of lipid, Glu, and amino acid metabolism in the liver tissue of obese WT and Lep KO mice. Full article

Animal studies are typically utilized to understand the complex mechanisms associated with toxicant-induced hepatotoxicity. Among the alternative approaches to animal studies, in vitro pooled human hepatocytes have the potential to capture population variability. Here, we examined the effect of the hepatotoxicant thioacetamide on pooled human hepatocytes, divided into five lots, obtained from forty diverse donors. For 24 h, pooled human hepatocytes were exposed to vehicle, 1.33 mM (low dose), and 12 mM (high dose) thioacetamide, followed by RNA-seq analysis. We assessed gene expression variability using heat maps, correlation plots, and statistical variance. We used KEGG pathways and co-expression modules to identify underlying physiological processes/pathways. The co-expression module analysis showed that the majority of the lots exhibited activation for the bile duct proliferation module. Despite lot-to-lot variability, we identified a set of common differentially expressed genes across the lots with similarities in their response to amino acid, lipid, and carbohydrate metabolism. We also examined efflux transporters and found larger lot-to-lot variability in their expression patterns, indicating a potential for alteration in toxicant bioavailability within the cells, which could in turn affect the gene expression patterns between the lots. Overall, our analysis highlights the challenges in using pooled hepatocytes to understand mechanisms of toxicity. Full article

Ferroptosis has garnered attention as a potential approach to fight against cancer, which is characterized by the iron-driven buildup of lipid peroxidation. However, the robust defense mechanisms against intracellular ferroptosis pose significant challenges to its effective induction. In this paper, an effective gene delivery vehicle was developed to transport solute carrier family 7 member 11 (SLC7A11) shRNA (shSLC7A11), which downregulates the expression of the channel protein SLC7A11 and glutathione peroxidase 4 (GPX4), evoking a surge in reactive oxygen species production, iron accumulation, and lipid peroxidation in hepatocellular carcinoma (HCC) cells, and subsequently leading to ferroptosis. This delivery system is composed of an HCC-targeting lipid layer and esterase-responsive cationic polymer, a poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N} (PQDEA) condensed shSLC7A11 core (G−LPQDEA/shSLC7A11). After intravenous (i.v.) injection, G−LPQDEA/shSLC7A11 quickly accumulated in the tumor, retarding its growth by 77% and improving survival by two times. This study is the first to construct a gene delivery system, G−LPQDEA/shSLC7A11, that effectively inhibits HCC progression by downregulating SLC7A11 expression. This underscores its therapeutic potential as a safe and valuable candidate for clinical treatment. Full article

Extracellular vesicles (EVs) are lipid membrane-enclosed particles produced by most cells, playing important roles in various biological processes. They have been shown to be involved in antiviral mechanisms such as transporting antiviral molecules, transmitting viral resistance, and participating in antigen presentation. While viral transmission was traditionally thought to occur through independent viral particles, the process of viral infection is complex, with multiple barriers and challenges that viruses must overcome for successful infection. As a result, viruses exploit the intercellular communication pathways of EVs to facilitate cluster transmission, increasing their chances of infecting target cells. Viral vesicle transmission offers two significant advantages. Firstly, it enables the collective transmission of viral genomes, increasing the chances of infection and promoting interactions between viruses in subsequent generations. Secondly, the use of vesicles as vehicles for viral transmission provides protection to viral particles against environmental factors, while also expanding the cell tropism allowing viruses to reach cells in a receptor-independent manner. Understanding the role of EVs in viral transmission is crucial for comprehending virus evolution and developing innovative antiviral strategies, therapeutic interventions, and vaccine approaches. Full article

Extracellular vesicles (EVs) are lipid-membrane-bound structures produced naturally by all cells and have a variety of functions. EVs act as vehicles for transporting important molecular signals from one cell to another. Several parasites have been shown to secrete EVs, and their biological functions have been extensively studied. EVs have been shown to facilitate communication with the host cells (such as modulation of the host’s immune system or promoting attachment and invasion into the host cells) or for communication between parasitic cells (e.g., transferring drug-resistance genes or factors modulating stage conversion). It is clear that EVs play an important role in host–parasite interactions. In this review, we summarized the latest research on the EVs secreted by protozoan parasites and their role in host–parasite and parasite–parasite communications. Full article

We have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects are abolished after serum depletion of EVs. RNA-seq analysis of the choroid plexus demonstrates EV-mediated effects on genes involved in barrier function and trans-barrier transport. Comparing the differentially expressed genes to recently published chronological aging clock genes reveals a reversal of transcriptomic aging in the choroid plexus. Following young serum treatment, the hippocampal transcriptome demonstrates significant upregulation of the anti-aging gene Klotho, along with an abrogated effect after EV depletion. Transcriptomic profiling of Klotho knockout and heterozygous mice shows the downregulation of genes associated with transport, exocytosis, and lipid transport, while upregulated genes are associated with activated microglia. The results of our study indicate the significance of EVs as vehicles to deliver signals from the periphery to the brain and the importance of Klotho in maintaining brain homeostasis. Full article

Extracellular vesicles (EVs) are cell-derived nano-sized lipid membranous structures that modulate cell–cell communication by transporting a variety of biologically active cellular components. The potential of EVs in delivering functional cargos to targeted cells, their capacity to cross biological barriers, as well as their high modification flexibility, make them promising drug delivery vehicles for cell-free therapies. Mesenchymal stromal cells (MSCs) are known for their great paracrine trophic activity, which is largely sustained by the secretion of EVs. MSC-derived EVs (MSC-EVs) retain important features of the parental cells and can be bioengineered to improve their therapeutic payload and target specificity, demonstrating increased therapeutic potential in numerous pre-clinical animal models, including in the treatment of cancer and several degenerative diseases. Here, we review the fundamentals of EV biology and the bioengineering strategies currently available to maximize the therapeutic value of EVs, focusing on their cargo and surface manipulation. Then, a comprehensive overview of the methods and applications of bioengineered MSC-EVs is presented, while discussing the technical hurdles yet to be addressed before their clinical translation as therapeutic agents. Full article

Exosomes are a group of vesicles that package and transport DNA, RNA, proteins, and lipids to recipient cells. They can be derived from blood, saliva, urine, and/or other biological tissues. Their impact on several diseases, such as neurodegenerative, autoimmune, and ocular diseases, have been reported, but not fully unraveled. The exosomes that are derived from saliva are less studied, but offer significant advantages over exosomes from other sources, due to their accessibility and ease of collection. Thus, their role in the pathophysiology of diseases is largely unknown. In the context of ocular diseases, salivary exosomes have been under-utilized, thus creating an enormous gap in the literature. The current review discusses the state of exosomes research on systemic and ocular diseases and highlights the role and potential of salivary exosomes as future ocular therapeutic vehicles. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell–cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA. Full article