ABSTRACT
AIM: We explored the role of miR-29b expression in endometrial cancer (EC) progression and patient prognosis. MATERIALS & METHODS: Patients with primary or metastatic EC (n = 356), patients with endometrial benign tumors (n = 149) and healthy female subjects (n = 155) were collected. We assessed the diagnostic value of miR-29b expression for EC using a receiver operating characteristic curve. RESULTS: The miR-29b expressions were lower in patients with primary or metastatic EC. Using miR-29b expression to diagnose EC produced 0.976 area under the curve, 96.1% sensitivity and 97.9% specificity. Cox proportional hazard regression model verified a low miR-29b expression and is an unfavorable prognostic indicator for EC. CONCLUSION: We conclude that downregulated miR-29b expression correlates with poor EC prognosis and is helpful to evaluate the EC prognosis.
Subject(s)
Biomarkers, Tumor/blood , Endometrial Neoplasms/blood , MicroRNAs/blood , Adult , Aged , Biomarkers, Tumor/metabolism , Disease Progression , Down-Regulation , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/metabolism , Middle Aged , Prognosis , ROC Curve , Sensitivity and SpecificityABSTRACT
Streptococcus pneumoniae is an important pathogen accounting for a large number of deaths worldwide. Due to drawbacks of the current polysaccharide-based vaccine, the most promising way to generate an improved vaccine may be to utilize protection-eliciting pneumococcal proteins. Pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA) are two vaccine candidates which have been evaluated against S. pneumoniae infection in animal models or human clinical trials with encouraging results. In this study, the efficacy of the fusion protein PsaA-PspA, which includes PsaA part and PspA part, in inducing immunoprotective effects against fatal pneumococcal challenge was evaluated in an animal model. PspA part of PsaA-PspA fusion protein contains both family1 N-terminal region and family 2 N-terminal clade-defining region of PspA. Immunization with the PsaA-PspA fusion protein induced high levels of antibodies against both PsaA and PspA, which could bind to intact S. pneumoniae strains bearing different PspAs. Ex vivo stimulation of splenocytes from mice immunized with PsaA-PspA induced IL-17A secretion. Mice immunized with PsaA-PspA showed reduced S. pneumoniae levels in the blood and lungs compared with the PBS group after intranasal infection. Finally, mice immunized with PsaA-PspA fusion proteins were protected against fatal challenge with pneumococcal strains expressing different PspAs regardless of the challenge route. These results support the PsaA-PspA fusion protein as a promising vaccine strategy, as demonstrated by its ability to enhance the immune response and stimulate production of high titer antibodies against S. pneumoniae strains bearing heterologous PspAs, as well as confer protection against fatal challenge with PspA family 1 and family 2 strains.
Subject(s)
Adhesins, Bacterial/immunology , Antibodies, Bacterial/biosynthesis , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Lipoproteins/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/immunology , Streptococcus pneumoniae/immunology , Adhesins, Bacterial/genetics , Animals , Antibodies, Bacterial/immunology , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Drug Evaluation, Preclinical , Female , Interleukin-17/metabolism , Lipoproteins/genetics , Lymphocytes/metabolism , Mice , Mice, Inbred BALB C , Peptide Fragments/genetics , Peptide Fragments/immunology , Rabbits , Recombinant Fusion Proteins/immunology , Spleen/cytology , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/pathogenicity , Vaccination , Vaccines, Synthetic/immunology , VirulenceABSTRACT
Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) have caused severe epidemics of hand, foot and mouth disease (HFMD) in the Asia Pacific in recent years, particularly in infants and young children. This disease has become a serious public health problem, as no vaccines or antiviral drugs have been approved for EV71 and CA16 infections. In this study, we compared four monovalent vaccines, including formalin-inactivated EV71 virus (iEV71), EV71 virus-like particles (VLPs) (vEV71), formalin-inactivated CVA16 virus (iCVA16) and CVA16 VLPs (vCVA16), along with two bivalent vaccines, including equivalent doses of formalin-inactivated EV71+CVA16 virus (iEV71+iCVA16) and EV71+CVA16 VLPs (vEV71+vCVA16). The IgG titers and neutralization antibodies titers demonstrated that there are no immune interference exists between the two immunogens of EV71 and CVA16. IgG subclass isotyping revealed that IgG1 and IgG2b were induced primarily in all vaccine groups. Furthermore, cross-neutralization antibodies were elicited in mouse sera against other sub-genotypes of EV71 and CVA16. In vivo challenge experiments showed that the immune sera from vaccinated animals could confer passive protection to newborn mice against lethal challenge with 14 LD50 of EV71 and 50 LD50 of CVA16. Our results indicated that bivalent vaccination is promising for HFMD vaccine development. With the advantage of having a better safety profile than inactivated virus vaccines, VLPs should be used to combine both EV71 and CVA16 antigens as a candidate vaccine for prevention of HFMD virus transmission.
