Zobrazení zdroje stránky Bowdenrasmussen0100

Nitrite stress is a major environmental factor that limits aquatic animal growth, reproduction and survival. Even so, some shrimp can withstand somewhat high concentrations of nitrite environment as our previous studies indicated. Therefore, we hypothesized that these shrimps might have specific adaptive strategies to adapt to high concentrations of nitrite environment. To identify the genes and pathways involved in the regulation of nitrite tolerance, we performed comparative transcriptomic analysis in the Litopenaeus vannamei nitrite-tolerant (NT) and nitrite-sensitive (NS) families, and untreated shrimps were used as the control group. After 24 h of nitrite exposure (NaNO2, 112.5 mg/L), a total of 1521 and 868 differentially expressed genes (DEGs) were obtained from NT compared with NS and control group, respectively. Functional enrichment analysis revealed that most of these DEGs were involved in immune defense, energy metabolism processes and endoplasmic reticulum (ER) stress. Nitrite stress significantly enhanced energy metabolism in NT by activating the expression of genes encoding key enzymes in oxidative phosphorylation (OXPHOS) pathway and tricarboxylic acid (TCA) cycle. Furthermore, some DEGs involved in innate immunity- related genes and pathways, and ER stress responses were highly expressed in NT. Therefore, we speculate that accelerated energy metabolism, higher expression of immunity and ER related genes might be the important adaptive strategies for NT in relative to NS under nitrite stress. These results will provide new sights on the potential tolerant molecular mechanisms and the breeding of new varieties of nitrite tolerant L. vannamei, with possible implications for other aquatic animals.Bisphenol A (BPA) is a well-known plasticizer, which is widely distributed in the aquatic environment. Lots of studies showed that BPA could lead to lipid metabolism disorder in fish, but few studies studied the mechanism from the perspective of lipid transport. Apolipoprotein A1 (ApoA1) is the main component of high-density lipoprotein (HDL), and plays important roles in reverse cholesterol transport (RCT). In this study, we investigated the effect and molecular mechanism of BPA on ApoA1 and its effect on cholesterol in adult male rare minnow. Results showed that BPA could disturb hepatic ApoA1 expression through regulating Esrrg recruitment and DNA methylation in its promoter region, and ultimately up-regulated ApoA1 protein levels. The increased hepatic ApoA1 improved HDL-C levels, enhanced RCT, and disrupted cholesterol levels. The present study reveals the effect and mechanism of BPA on fish cholesterol metabolism from the perspective of cholesterol transport.Malaria elimination means cessation of parasite transmission. At present, the declining malaria incidence in many countries has made elimination a feasible goal. Transmission control has thus been placed at the center of the national malaria control programs. [https://www.selleckchem.com/products/mcc950-sodium-salt.html MCC950 cell line] The efficient transmission of Plasmodium vivax from humans to mosquitoes is a key factor that helps perpetuate malaria in endemic areas. A better understanding of transmission is crucial to the success of elimination efforts. Biological delineation of the parasite transmission process is important for identifying and prioritizing new targets of intervention. Identification of the infectious parasite reservoir in the community is key to devising an effective elimination strategy. Here we describe the fundamental characteristics of P. vivax gametocytes - the dynamics of their production, longevity, and the relationship with the total parasitemia - as well as recent advances in the molecular understanding of parasite sexual development. In relation to malaria elimination, factors influencing the human infectivity and the current evidence for a role of asymptomatic carriers in transmission are presented.<br /><br /> Decreased childhood vaccination can lead to local outbreaks of vaccine-preventable disease. In a pilot study from our group, 72% of parents of newborns reported initiating their vaccine decision-making for that child prior to conception. Since a sound understanding of the timing of parental vaccine decision-making is needed to direct educational efforts, we surveyed a national cohort of first-time parents to extend our preliminary findings.<br /><br /> From March 2019-March 2020, first-time parents of newborns in mother-baby units of the Better Outcomes through Research for Newborns (BORN) network completed the Vaccine Preference Development Survey (VPDS). The VPDS measures intent to vaccinate, timing of vaccine decision-making, and sources of influence. Univariate and multivariate analyses explored associations between intent to vaccinate and timing of vaccine decision-making with demographic variables.<br /><br /> Twenty-three sites provided surveys through site-specific nonrandom systemic sampling; 91% (1393/1524) of surveys were used in the analysis. link2 Most parents planned to fully vaccinate (1191/1380, 86.3%) and started vaccine decision-making prior to conception (850/1378, 61.7%). Maternal age, race and ethnicity, relationship status, and education were all significantly associated with planning to fully vaccinate and preconception decision-making (p&lt;0.001). Preconception decision-making correlated strongly with intent to fully vaccinate (p&lt;0.001). Parents influenced by personal education, medical professionals, and family/friends were more likely to endorse preconception decision-making; those strongly influenced by internet/social media were less likely to allow all vaccines or start decision-making prior to conception.<br /><br /> Vaccine decision-making occurs preconception for most new parents. Initiating vaccine discussions during the birth hospitalization may be too late.<br /><br />Vaccine decision-making occurs preconception for most new parents. Initiating vaccine discussions during the birth hospitalization may be too late.<br /><br /> Obesity is globally recognized as a critically important disease by professional medical organizations in addition to the World Health Organization and American Medical Association, but the health care systems, medical teams, and the public have been slow to embrace this concept.<br /><br /> American Association of Clinical Endocrinology (AACE) staff drafted the survey, and two endocrinologists independently reviewed the survey questions and modified the survey instrument. The survey included inquiries related to practice and patient demographics, awareness of obesity, treatment of obesity, barriers to improving obesity outcomes, digital health, cognitive behavioral therapy, lifestyle medicine, anti-obesity medications, weight stigma, and social determinants of health. The survey was emailed to 493 endocrinologists, with 305 completing the study (62%).<br /><br /> Ninety-eight percent of the responders agree that obesity is a disease, while 2% neither agree nor disagree. 53% of respondents are familiar with the term "adiposityians, identify knowledge gaps and create educational tools to address those gaps.The goal of this study was to evaluate hepatocyte-specific gene editing, via systemic administration of hyaluronic acid (HA)-based nanoparticles in naïve CD-1 mice. Using HA-poly(ethylene imine) (HA-PEI) and HA-PEI-mannose nanoparticles with differential mannose density (1X and 2X), we have evaluated systemic biodistribution and hepatocyte-specific delivery using IVIS imaging and flow cytometry. link3 Additionally, we have investigated hepatocyte-specific delivery and transfection of CRISPR/Cas9 gene editing plasmid and eGFP gene payload to integrate at the Rosa26 locus. IVIS imaging showed uptake of HA-PEI nanoparticles primarily by the liver, and with addition of mannose at different concentrations, the nanoparticles showed increased uptake in both the liver and spleen. HA-PEI-mannose nanoparticles showed 55-65% uptake by hepatocytes, along with uptake by resident macrophage regardless of the mannose concentration. One of two gRNA targets showed 15% genome editing and obtained similar results for all three nanoparticle formulations. Cells positive for our gene payload were greatest with HA-PEI-mannose-1X nanoparticles where 16.2% of cells were GFP positive. The results were encouraging as proof of concept for the development of a non-viral biodegradable and biocompatible polymeric delivery system for gene editing specifically targeting hepatocytes upon systemic administration.Tolerance induction is central to the suppression of autoimmunity. Here, we engineered the preferential uptake of nano-conjugated autoantigens by spleen-resident macrophages to re-introduce self-tolerance and suppress autoimmunity. The brain autoantigen, myelin oligodendrocyte glycoprotein (MOG), was conjugated to 200 or 500nm silica nanoparticles (SNP) and delivered to the spleen and liver-resident macrophages of experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis. MOG-SNP conjugates significantly reduced signs of EAE at a very low dose (50μg) compared to the higher dose (&gt;800μg) of free-MOG. This was associated with reduced proliferation of splenocytes and pro-inflammatory cytokines secretion, decreased spinal cord inflammation, demyelination and axonal damage. Notably, biodegradable porous SNP showed an enhanced disease suppression assisted by elevated levels of regulatory T cells and programmed-death ligands (PD-L1/2) in splenic and lymph node cells. Our results demonstrate that targeting nano-conjugated autoantigens to tissue-resident macrophages in lymphoid organs can effectively suppress autoimmunity.Proprotein convertase subtilisin/kexin type 9 is a protease enzyme secreted by liver that downregulates hepatic low-density lipoprotein receptor (LDLR) by binding and chaperoning LDLR to lysosomes for degradation, causing hypercholesteremia. The development of anti-PCSK9therapeutics attracted considerable attention for the management of cardiovascular disease risk. However, only subcutaneous injectable PCSK9 monoclonal antibodies have been FDA approved. Oral administration of small-molecule PCSK9 inhibitors has the potential to become a practical therapeutic option if achievable. In the present work, we used nanotechnological approaches to develop the first small oral molecule nano-hepatic targeted anti-PCSK9. Using high-throughput optimization and a series of evaluations, a stable water-dispersible 150-200nm nano-encapsulated drug (named P-4) conjugated with hepatic targeting moiety was synthesized and characterized (named P-21). Pharmacodynamic (PD), pharmacokinetic (PK) and bioavailability studies were conducted using a high fat diet nutritionally induced hypercholesterolemia mouse model to evaluate the efficacy of P-21 as an anti-PCSK9 LDL-cholesterol lowering hepatic targeted nanodrug. The PD results demonstrate that P-21 in a dose-dependent manner is highly effective in lowering LDL-C by 50-90%. PK results show the maximum plasma concentration (Cmax) of P-4 was observed after 30min of administration with 31% oral bioavailability and had a sustained longer half-life up to 24h. In vivo safety studies in rats showed no apparent adverse effects, normal chemical biomarkers and normal histopathological findings in all P-21 treated groups at different escalating doses. Compared to the FDA-approved monoclonal antibodies, P-21 offers a more efficient, and practical treatment protocol for targeting uncontrolled hypercholesterolemia in reducing the risk of cardiovascular diseases. The present study introduced a nano-targeted drug delivery approaches for PCSK9/LDLR antagonist.