Vazquezcurtis2659

Targeted P-NLCs enhanced the cytotoxicity and cellular uptake compared to untargeted NLCs. Furthermore, PIP-P-NLCs improved in vivo anticancer effect of PIP as proved by histological examination of liver tissues, suppression of liver enzymes and oxidative stress environment in the liver, and alteration of cell cycle regulators. To conclude, PIP-P-NLCs can act as a promising approach for targeted delivery of PIP to hepatocellular carcinoma.Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are widely-investigated vaccine adjuvants owing to their safety, antigen slow-release ability, and good adjuvants activity. This study involved the preparation of the polyethyleneimine-modified immunopotentiator Alhagi honey polysaccharide encapsulated PLGA nanoparticles (PEI-AHPP) and the assembly of the Pickering emulsion with PEI-AHPP as shell and squalene as core (PEI-PPAS). Furthermore, PEI-AHPP and PEI-PPAS were characterized. To assess the strength and type of immune responses induced by different adjuvants, the chickens were immunized with H9N2-absorbed nanoparticle formulations. Our results showed that since the PEI-PPAS possess rough strawberry-like surfaces, a large number of antigens can be absorbed on their surfaces through simple mixing. Compared to PEI-AHPP, PEI-PPAS was found to exhibit better stability and antigen-loading efficiency. The adjuvant activity of the nanoparticles showed PEI-PPAS/H9N2 to induce long-lasting and high Hemagglutination inhibition (HI) titers, high thymus, spleen, and organ index of the bursa of Fabricius. Moreover, the chickens immunized with PEI-PPAS/H9N2 showed a mixture of high CD4+ and CD8a+ T-cells in the spleen and strong Th1 and Th2-type cytokines secretion. Thus, these findings demonstrated PEI-PPAS to be a vaccine adjuvant inducing a mixed cellular and humoral immune response, which can potentially serve as an effective vaccine delivery adjuvant system for the H9N2 antigen.Recently, the pharmaceutical industry has been facing several challenges associated to the use of outdated development and manufacturing technologies. The return on investment on research and development has been shrinking, and, at the same time, an alarming number of shortages and recalls for quality concerns has been registered. The pharmaceutical industry has been responding to these issues through a technological modernization of development and manufacturing, under the support of initiatives and activities such as quality-by-design (QbD), process analytical technology, and pharmaceutical emerging technology. In this review, we analyze this modernization trend, with emphasis on the role that mathematical modeling plays within it. We begin by outlining the main socio-economic trends of the pharmaceutical industry, and by highlighting the life-cycle stages of a pharmaceutical product in which technological modernization can help both achieve consistently high product quality and increase return on investment. Then, we review the historical evolution of the pharmaceutical regulatory framework, and we discuss the current state of implementation and future trends of QbD. The pharmaceutical emerging technology is reviewed afterwards, and a discussion on the evolution of QbD into the more effective quality-by-control (QbC) paradigm is presented. Further, we illustrate how mathematical modeling can support the implementation of QbD and QbC across all stages of the pharmaceutical life-cycle. In this respect, we review academic and industrial applications demonstrating the impact of mathematical modeling on three key activities within pharmaceutical development and manufacturing, namely design space description, process monitoring, and active process control. Finally, we discuss some future research opportunities on the use of mathematical modeling in industrial pharmaceutical environments.Mitochondria play a central role in several important cellular processes such as energy production, apoptosis, fatty acid catabolism, calcium regulation, and cellular stress response. Multiple nuclear transcription factors have been reported for their role in the regulation of mitochondrial gene expression. More recently, the role of the forkhead family of transcription factors in various mitochondrial pathways has been reported. Among them, FOXO1, FOXO3a, FOXG1, and FOXM1 have been reported to localize to the mitochondria, of which the first two have been observed to bind to the mitochondrial D-loop. This suggests an important role for forkhead transcription factors in the direct regulation of the mitochondrial genome and function. Forkheads such as FOXO3a, FOXO1, and FOXM1 are involved in the cellular response to oxidative stress, hypoxia, and nutrient limitation. Several members of the forkhead family of transcription factors are also involved in the regulation of nuclear-encoded genes associated with the mitochondrial pathway of apoptosis, respiration, mitochondrial dynamics, and homeostasis.Li-Fraumeni and Li-Fraumeni-like syndromes (LFS/LFL) are hereditary cancer predisposition disorders associated with germline mutations in the TP53 tumor suppressor gene. Here, we stably expressed LFS/LFL-associated p53 mutants R337H and G245S in p53-null H1299 cells to study their cellular and molecular effects. Mutant proteins showed distinct oligomerization states and opposing effects on cell proliferation and viability. Stable expression of p53G245S enhanced cell proliferation and spheroid formation, while cells stably expressing p53R337H showed reduced proliferation and clonogenicity, along with increased cell death. Mass spectrometry analysis revealed that proteins whose expression was induced by p53R337H or p53G245S expression were related to distinct metabolic profiles. Proteins upregulated by p53G245S expression were associated with a Warburg phenotype, while proteins upregulated by p53R337H expression were related to oxidative phosphorylation and fatty acid oxidation. Differences in mitochondrial mass and activity between cells stably expressing p53R337H or p53G245S were further corroborated by High Resolution Respirometry, flow cytometry and qPCR assays. The implications of the different oncogenic properties of p53R337H and p53G245S on the clinical manifestation and treatment of LFS/LFL patients carrying these mutations are discussed.Heparinases are enzymes that selectively cleave heparin and heparan sulfate chains, via cleavage of the glycosidic linkage between hexosamines and uronic acids, producing disaccharide and oligosaccharide products. While heparin is well known as an anti-coagulant drug, heparin and heparan sulfate are also involved in biological processes such as inflammation, cancer and angiogenesis and viral and bacterial infections and are of growing interest for their therapeutic potential. Recently, potential roles of heparin and heparan sulfate in relation to COVID-19 infection have been highlighted. The ability of heparinases to selectively cleave heparin chains has been exploited industrially to produce low molecular weight heparin, which has replaced heparin in several clinical applications. Other applications of heparinases include heparin and heparan sulfate structural analysis, neutralisation of heparin in blood and removal of the inhibitory effect of heparin on various enzymes. Heparinases are known to inhibit neovascularization and heparinase III is of interest for treating cancer and inhibiting tumour cell growth. Heparinase activity, first isolated from Pedobacter heparinus, has since been reported from several other microorganisms. Significant progress has been made in the production, characterisation and improvement of microbial heparinases in response to application demands in terms of heparinase yield and purity, which is likely to extend their usefulness in various applications. This review focuses on recent developments in the identification, characterisation and improvement of microbial heparinases and their established and emerging industrial, clinical and therapeutic applications.Hypoxia ( less then 2 mg O2/L) is one of the main environmental stressors that affects aquatic organisms, including the white shrimp (Litopenaeus vannamei). During hypoxia, reactive oxygen species (ROS) accumulation induces oxidative stress and damage to biomolecules. Redox state and ROS overproduction are modulated by the antioxidant system that is composed of several antioxidant enzymes, proteins, and other small compounds. Glutathione peroxidase 4 (GPx4) has emerged as an important antioxidant enzyme with cytoprotective roles. In vertebrates, antioxidant and pro-oxidant stress responses are regulated by several factors, including the p53 protein. However, little is known about GPx4 responses in crustaceans and the regulation by p53. Herein we analyzed and characterized the L. vannamei GPx4 and evaluated the responses to hypoxia and p53 knock-down. We found a unique GPx4 gene that produces five transcript variants (TVs) and only two protein isoforms with distinct cellular localization. GPx4 expression in hepatopancreas during hypoxia and p53 knock-down changed during short and long-term hypoxia, suggesting that GPx4 may be a sensitive indicator of antioxidant imbalance during stress. Zoligratinib order Knock-down of p53 induced a reduction in GPx4 expression, indicating that p53 modulates GPx4 responses during stress. This agrees with our findings of putative consensus sequences for p53 in the GPx4 gene promoter by in silico analysis. Also, the antioxidant response was effective in preventing major protein damage during hypoxia since no changes were detected in carbonylated proteins content in hepatopancreas during hypoxia. Conversely, p53 knock-down produced significant changes in carbonylated proteins.

Polygonatum sibiricum, known as "Huangjing" in Chinese traditional medicine, of which functions include invigorating Qi and nourishing Yin, tonifying spleen and kidney, which are considered to replenish energy, and strengthen immunity. However, both the active components and mechanism of the immune-enhancing effect of Polygonatum sibiricum have not been clarified.

To evaluate the immunoregulation effects of PSE30 (Polygonatum sibiricum ethanol 30) and PSE75 (Polygonatum sibiricum ethanol 75). The gut microbial and activation of RAW264.7cells were also evaluated for exploring the mechanism of PSE75.

Female ICR mice were randomly divided into different groups, which were pretreated with 0.9% saline, Yupingfeng granules, different dosage of PSE30 or PSE75. And the immunosuppressed mice model was constructed using cyclophosphamide. And the total duration of the experiment was 15d. After that, the serum Immunoglobulins G (IgG) and Immunoglobulins M (IgM) antibody, regular blood testing, assessment of naturalurbed by cyclophosphamide. PSE75 could markedly promote the secretion of IL-6, IL-10, and IL-12 p40 from RAW264.7cell (P＜0.01, or P＜0.001).

PSE75 was proved to be a more promising immunomodulation agent, of which may enhance the immunity of immunosuppressed mice by improving gut microbial and activating macrophages. And PSE75 could be developed as a good immune booster in the future.

PSE75 was proved to be a more promising immunomodulation agent, of which may enhance the immunity of immunosuppressed mice by improving gut microbial and activating macrophages. And PSE75 could be developed as a good immune booster in the future.