Bullockkirk7746

EVs have great potential to be further developed as diagnostic, immunomodulation and therapeutic alternatives to fill the knowledge gaps in the current parasitic diseases discussed in this review. Nanomedicine and vaccine development could be explored, with the utilization and/or modification of the parasitic EVs as novel treatment and prevention strategies.Plasma high density lipoprotein (HDL) exhibits many functions that render it an effective endothelial protective agent and may underlie its potential role in protecting the maternal vascular endothelium during pregnancy. In non-pregnant individuals, the HDL lipidome is altered in metabolic disease compared to healthy individuals and is linked to reduced cholesterol efflux, an effect that can be reversed by lifestyle management. Specific sphingolipids such as sphingosine-1-phosphate (S1P) have been shown to mediate the vaso-dilatory effects of plasma HDL via interaction with the endothelial nitric oxide synthase pathway. This review describes the relationship between plasma HDL and vascular function during healthy pregnancy and details how this is lost in pre-eclampsia, a disorder of pregnancy associated with widespread endothelial dysfunction. Evidence of a role for HDL sphingolipids, in particular S1P and ceramide, in cardiovascular disease and in healthy pregnancy and pre-eclampsia is discussed. Available data suggest that HDL-S1P and HDL-ceramide can mediate vascular protection in healthy pregnancy but not in preeclampsia. HDL sphingolipids thus are of potential importance in the healthy maternal adaptation to pregnancy.Disruption of circadian (~24 h) rhythms is associated with an increased risk of cardiometabolic diseases. Therefore, unravelling how circadian rhythms are regulated in different metabolic tissues has become a prominent research focus. Of particular interest is brown adipose tissue (BAT), which combusts triglyceride-derived fatty acids and glucose into heat and displays a circannual and diurnal rhythm in its thermogenic activity. In this review, the genetic, neuronal and endocrine generation of these rhythms in BAT is discussed. In addition, the potential risks of disruption or attenuation of these rhythms in BAT, and possible factors influencing these rhythms, are addressed.Reproductive transition of grasses is characterized by switching the pattern of lateral branches, featuring the suppression of outgrowth of the subtending leaves (bracts) and rapid formation of higher-order branches in the inflorescence (panicle). However, the molecular mechanisms underlying such changes remain largely unknown. Here, we show that bract suppression is required for the reproductive branching in rice. We identified a pathway involving the intrinsic time ruler microRNA156/529, their targets SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) genes, NECK LEAF1 (NL1), and PLASTOCHRON1 (PLA1), which regulates the bract outgrowth and thus affects the pattern switch between vegetative and reproductive branching. Suppression of the bract results in global reprogramming of transcriptome and chromatin accessibility following the reproductive transition, while these processes are largely dysregulated in the mutants of these genes. These discoveries contribute to our understanding of the dynamic plant architecture and provide novel insights for improving crop yields.Chemoresistance is a major factor driving cancer recurrence. This study investigated the potential of zebularine, a dual cytidine deaminase (CDA)/epigenetic inhibitor, to circumvent gemcitabine-resistance in pancreatic cancer using a nanomedicine co-delivery approach. The mRNA expression of key metabolic enzymes, including CDA for gemcitabine deactivation in a gemcitabine-resistant cell line Gr2000 and its parental MIA PaCa-2 was compared using quantitative reverse transcription polymerase chain reaction. A highly gemcitabine-resistant population (HRP) in Gr2000 were characterised for their growth pattern, β-galactosidase activity (a hallmark of senescence) and chemosensitivity to zebularine after isolation. The CDA inhibition effects of zebularine on the intracellular gemcitabine accumulation and pharmacokinetics in rats when co-delivered with pH-sensitive liposomes (pSL) were investigated. Gr2000 had a 3-time upregulated mRNA expression and enzyme activity for CDA. The HRP (28% of bulk Gr2000) were predominately senescent cells which re-proliferated following a growth arrest for a week. Zebularine suppressed the regrowth of senescent cells, meanwhile enhanced cellular gemcitabine concentration by 2-fold. When co-delivered with pSL, zebularine increased cellular gemcitabine concentration by 4-fold, and extended the half-life of gemcitabine in plasma by 22-fold in rats. In conclusion, multiple mechanisms including therapy-induced senescence were identified with gemcitabine-resistance. Co-delivery of zebularine using liposomes could provide multifaceted benefits in gemcitabine therapy for pancreatic cancer treatment.PEGylated Liquisomes (P-Liquisomes), a novel drug delivery system was designed for the first time by incorporating phospholipid complex in PEGylated liquid crystalline nanoparticles (P-LCNPs). L-carnosine (CN), a challenging dipeptide, has proven to be a promising anti-cancer drug. However, it exhibits high water solubility and extensive in-vivo degradation that halts its use. The objective of this work was to investigate the ability of our novel system to improve the CN anticancer activity by prolonging it's release and protecting it in-vivo. In-vitro appraisal revealed spherical light-colored vesicles encapsulated in the liquid crystals, confirming the successful formation of the combined system. P-Liquisomes were nano-sized (149.3 ± 1.4 nm), with high ZP (-40.2 ± 1.5 mV), complexation efficiency (97.5 ± 0.9%) and outstanding sustained release of only 75.4% released after 24 h, compared to P-LCNPs and Phytosomes. The results obtained with P-Liquisomes are considered as a break through compared to P-LCNPs or Phytosomes alone, especially when dealing with the hydrophilic CN. In-vitro cytotoxicity evaluation, revealed superior cytotoxic effect of P-Liquisomes (IC50 = 25.9) after 24 h incubation. Besides, P-Liquisomes proved to be non-toxic in-vivo and succeeded to show superior chemopreventive activity manifested by reduction of; % tumor growth (7.1%), VEGF levels (14.3 pg/g tissue), cyclin D1 levels 15.5 ng/g tissue and elevation in caspase-3 level (36.4 ng/g tissue), compared to Phytosomes and CN solution. Conclusively, P-Liquisomes succeded to achieve the maximum therapeutic outcome of CN without altering its activity and might be used as a sustained delivery system for other promising hydrophilic compounds.Stem cell treatment is promising in the various disorders treatment, but its effect is confined by the adverse conditions in the damaged tissues. The utilization of hydrogels has been suggested as a procedure to defeat this issue by developing the engraftment and survival of injected stem cells. Specifically, injectable hydrogels have drawn much attention due to their shape adaptability, ease of use, and the capability to reach body parts that are hard to access. In this study, the thermosensitive injectable hydrogels based on oxidized alginate, gelatin, and carbon nitride quantum dots (CNQDs) have been fabricated for tissue engineering. The mechanical characteristics of the nanocomposite hydrogels were investigated by rheology analysis. The results show that increasing the amount of CNQDs improve the mechanical strength of the nanocomposite hydrogels. The Cross-section morphology of freeze dried hydrogels comprising 0.25, 1.5, and 3.0% CNQDs indicate porous structure with interrelated pores. Besides, the result of in vitro degradation reveals that the hydrogels comprising CNQDs are more durable than the one without CNQDs. A reduction in the biodegradation and swelling ratio is perceived with the addition of CNQDs. The cell viability and attachment show that the nanocomposite hydrogels are biocompatible (>88%) with great cell adhesion to osteosarcoma cell line MG63 depending on the presence of CNQDs.Topical and transdermal delivery of vancomycin hydrochloride (VH), a broad-spectrum peptide antibiotic, is a challenge because of its high molecular weight (1485.7 Da) and hydrophilicity (log P -3.1). The objective of this study was to investigate the feasibility of delivering VH into and across the skin using permeation enhancement techniques. Skin permeation studies were performed using Franz diffusion cell apparatus in the excised porcine skin model. The influence of co-treatment and pre-treatment of chemical permeation enhancers (oleic acid and palmitic acid) on permeation of VH across intact and tape-stripped skin was evaluated. In addition, continuous anodal iontophoresis was applied to enhance the skin permeation of VH. The mechanism of skin permeation enhancement by palmitic acid was investigated using FTIR spectroscopy, impedance spectroscopy, and thermal analysis techniques. Pharmacokinetic analysis was performed after the topical application of VH formulations in Sprague Dawley rats. Results from pape-stripped skin compared with free VH on intact skin. Taken together, VH can be delivered through the topical route using a combination of chemical enhancer and tape-stripping to treat local and systemic bacterial infections.In the absence of an effective vaccine, vaginal microbicides are essential for preventing the sexual transmission of HIV to women. Antiretroviral vaginal films have emerged as promising choices, especially those offering mucoadhesivity and controlled drug release. Tenofovir-loaded bilayer films based on Eudragit® L100 (EL100) and a biopolymer - gum arabic, karaya gum, pectin or tragacanth gum - were developed in a single-stage process. Cytotoxicity studies in three human cell lines indicated no toxicity of the excipients at the concentrations tested. Raman spectroscopy and SEM confirmed the formation of the two layers and their anchoring. Crenolanib mouse Texture analysis showed no major differences between the batches. The swelling of the film is conditioned by its biopolymer nature and by the amount of EL100, which acts as structuring agent thus enhancing swelling. Tragacanth gum-based batches showed high mucoadhesion regardless the amount of EL100. The controlled release of Tenofovir in simulated vaginal fluid was faster in the presence of simulated seminal fluid due to the dissolution of EL100. Films containing 400 mg of EL100 and tragacanth gum are promising candidates for future studies, as they could sexually safeguard women from HIV for at least one week and ensure greater protection during intercourse.The orally administrated antidepressants not only caused side effects such as dizziness, diarrhea, and drug resistance, but also worked slowly. Therefore, new antidepressants and preparations derived from natural medicines play an important role in the study of antidepressant drugs. It was reported that the two components of Zuojin pill, berberine (BBR) and evodiamine (EVO), were used in combination to improve depressive disorder. In our study, a self-assembled thermosensitive in-situ hydrogel was prepared to achieve sustained co-delivery of BBR and EVO. The preparation process of hydrogel consists of two steps, namely, the inclusion of the drugs and thermosensitive self-assembly of the hydrogel. In vitro experimental results indicated that the prepared hydrogel showed a good thermosensitive property under physiological temperature. The hydrogel had a slow and controlled release behavior for BBR and EVO, according with first-order equation. In vivo experimental results indicated that compared to intragastric administration of drug solution, the intranasal administration of hydrogel increased bioavailability of BBR and EVO, approximately 135 and 112 folds, respectively.