Study of environmentally sensitive polymeric carriers for controlled drug delivery

Ph.DDOCTOR OF PHILOSOPH

Comprehensive Analysis of Common Different Gene Expression Signatures in the Neutrophils of Sepsis

The central component of sepsis pathogenesis is inflammatory disorder, which is related to dysfunction of the immune system. However, the specific molecular mechanism of sepsis has not yet been fully elucidated. The aim of our study was to identify genes that are significantly changed during sepsis development, for the identification of potential pathogenic factors. Differentially expressed genes (DEGs) were identified in 88 control and 214 septic patient samples. Gene ontology (GO) and pathway enrichment analyses were performed using David. A protein-protein interaction (PPI) network was established using STRING and Cytoscape. Further validation was performed using real-time polymerase chain reaction (RT-PCR). We identified 37 common DEGs. GO and pathway enrichment indicated that enzymes and transcription factors accounted for a large proportion of DEGs; immune system and inflammation signaling demonstrated the most significant changes. Furthermore, eight hub genes were identified via PPI analysis. Interestingly, four of the top five upregulated and all downregulated DEGs were involved in immune and inflammation signaling. In addition, the most intensive hub gene AKT1 and the top DEGs in human clinical samples were validated using RT-PCR. This study explored the possible molecular mechanisms underpinning the inflammatory, immune, and PI3K/AKT pathways related to sepsis development

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

ABSTRACTCoxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality

Vitamin A Deficiency Impairs Mucin Expression and Suppresses the Mucosal Immune Function of the Respiratory Tract in Chicks

<div><p>The chicken immune system is immature at the time of hatching. The development of the respiratory immune system after hatching is vital to young chicks. The aim of this study was to investigate the effect of dietary vitamin A supplement levels on respiratory mucin and IgA production in chicks. In this study, 120 one-day-old broiler chicks were randomly divided into 4 groups consisting of three replicates of 10 broilers and subjected to dietary vitamin A supplement levels of 0, 1,500, 6,000, or 12,000 IU/kg for seven days. Compared with control birds, vitamin A supplementation significantly increased the mucin and IgA levels in the bronchoalveolar lavage fluid (BALF) as well as the IgA level in serum. In the lungs, vitamin A supplementation downregulated TNF-α and EGFR mRNA expression. The TGF-β and MUC5AC mRNA expression levels were upregulated by vitamin A supplementation at a dose of 6,000 IU/kg, and the IL-13 mRNA expression level was increased at the 12,000 IU/kg supplement level. Vitamin A deficiency (control) significantly decreased the mRNA expression levels of MUC2, IgA, EGFR, IL-13 and TGF-β in trachea tissue. Histological section analysis revealed that the number of goblet cells in the tracheal epithelium was less in the 0 and 12,000 IU/kg vitamin A supplement groups than in the other groups. In conclusion, vitamin A deficiency suppressed the immunity of the airway by decreasing the IgA and mucin concentrations in neonatal chicks. This study suggested that a suitable level of vitamin A is essential for the secretion of IgA and mucin in the respiratory tract by regulating the gene expression of cytokines and epithelial growth factors.</p></div

Gene-specific primer sequences used for gene transcription analyses of chicken.

<p>Gene-specific primer sequences used for gene transcription analyses of chicken.</p

Gasdermin D in macrophages drives orchitis by regulating inflammation and antigen presentation processes

Abstract Inflammation in the testes induced by infection and autoimmunity contributes significantly to male infertility, a public health issue. Current therapies using antibiotics and broad-spectrum anti-inflammatory drugs are ineffective against non-bacterial orchitis and induce side effects. This highlights the need to explore the pathogenesis of orchitis and develop alternative therapeutic strategies. In this study, we demonstrated that Gasdermin D (GSDMD) was activated in the testes during uropathogenic Escherichia coli (UPEC)-induced acute orchitis, and that GSDMD in macrophages induced inflammation and affected spermatogenesis during acute and chronic orchitis. In testicular macrophages, GSDMD promoted inflammation and antigen presentation, thereby enhancing the T-cell response after orchitis. Furthermore, the pharmacological inhibition of GSDMD alleviated the symptoms of UPEC-induced acute orchitis. Collectively, these findings provide the first demonstration of GSDMD’s role in driving orchitis and suggest that GSDMD may be a potential therapeutic target for treating orchitis

Effect of the dietary vitamin A supplemental levels (0, 1500, 6000, and 12000 IU/kg) on the IgA (A), MUC2 (B), and MUC5AC (C) mRNA expression levels in the trachea and lung tissue.

<p>Data are presented as the means ± SEM (n = 9); *: <i>P</i> < 0.05.</p

Ingredients and calculated analysis of experimental diets.

<p>^#\\Mineral and vitamin premix provided the followings per kilogram of diet: manganese, 100 mg; zinc, 75 mg; iron, 80 mg; iodine, 0.65 mg; copper, 80 mg; selenium, 0.35 mg; cholecalciferol, 0.002 MIU; vitamin E, 0.011 MIU; vitamin K, 1.0 mg; thiamine, 1.2 mg; riboflavin, 5.8 mg; niacin, 66 mg; pantothenic acid, 10 mg; pyridoxine, 2.6 mg; biotin, 0.10 mg; folic acid, 0.7 mg; and vitamin B₁₂, 0.012 mg.</p><p>Ingredients and calculated analysis of experimental diets.</p

origin software data

<p>Fig 1 Effect of dietary vitamin A supplemental levels(0, 1500, 6000, and 12000 IU/kg) on the serum IgA concentration</p> <p>Fig 2 Effect of dietary vitamin A supplemental levels on the mucin and IgA concentrations in BALF</p> <p>Fig 4 Effect of the dietary vitamin A supplemental levels on the IgA (A), MUC2 (B), and MUC5AC (C) mRNA expression levels in the trachea and lung tissue</p> <p>Fig 5 Effect of the dietary vitamin A supplemental levels on the TNF-α (A), IL-6 (B), IL-13 (C), TGF-α (D), TGF-β (E), and EGFR (F) mRNA expression levels in the trachea and lung tissue</p