No abstract available.
Leukemia*

Lyme disease is the most common vector-borne disease in the United States and Europe, caused by a tick-borne spirochete, Borrelia burgdorferi. Life cycle alternation between arthropod and mammals enhanced B. burgdorferi to adapt to two diverse niches. Although B. burgdorferi infection in these reservoir hosts appears asymptomatic, infection in human can typically cause inflammation in the skin, nervous system, musculoskeletal system and heart. In this review, we discuss the basic molecular characteristics and cell biology of B. burgdorferi and provide an overview of spirochete-induced activation of innate and adaptive immunity, resulting in particular immunopathology. Advancing understanding of the immune evasion mechanisms of B. burgdorferi provides important implications for ongoing research and clinical practice of Lyme disease.
Adaptive Immunity ; Arthropods ; Borrelia burgdorferi ; Europe ; Heart ; Humans ; Immune Evasion ; Inflammation ; Life Cycle Stages ; Lyme Disease* ; Mammals ; Musculoskeletal System ; Nervous System ; Skin ; Spirochaetales ; United States

Cellular replicative senescence is a major contributing factor to aging and to the development and progression of aging-associated diseases. In this study, we sought to determine viral replication efficiency of influenza virus (IFV) and Varicella Zoster Virus (VZV) infection in senescent cells. Primary human bronchial epithelial cells (HBE) or human dermal fibroblasts (HDF) were allowed to undergo numbers of passages to induce replicative senescence. Induction of replicative senescence in cells was validated by positive senescence-associated β-galactosidase staining. Increased susceptibility to both IFV and VZV infection was observed in senescent HBE and HDF cells, respectively, resulting in higher numbers of plaque formation, along with the upregulation of major viral antigen expression than that in the non-senescent cells. Interestingly, mRNA fold induction level of virus-induced type I interferon (IFN) was attenuated by senescence, whereas IFN-mediated antiviral effect remained robust and potent in virus-infected senescent cells. Additionally, we show that a longevity-promoting gene, sirtuin 1 (SIRT1), has antiviral role against influenza virus infection. In conclusion, our data indicate that enhanced viral replication by cellular senescence could be due to senescence-mediated reduction of virus-induced type I IFN expression.
Aging ; Cell Aging* ; Epithelial Cells ; Fibroblasts ; Herpesvirus 3, Human ; Humans ; Influenza, Human ; Interferon Type I ; Orthomyxoviridae ; RNA, Messenger ; Sirtuin 1 ; Up-Regulation

BACKGROUND: Weaning from mechanical ventilation is difficult in the intensive care unit (ICU). Many controversial questions remain unanswered concerning the predictors of weaning failure. This study investigates patient characteristics and delayed weaning after lung transplantation. METHODS: This study retrospectively reviewed the medical records of 17 lung transplantation patients from October 2012 to December 2013. Patients able to be weaned from mechanical ventilation within 8 days after surgery were assigned to an early group (n = 9), and the rest of the patients were assigned to the delayed group (n=8). Patients' intraoperative and postoperative characteristics were collected and analyzed, and conventional weaning predictors, including rapid shallow breathing index (RSBI), were also assessed. RESULTS: The results of the early group showed a significantly shorter ICU stay in addition to a shorter hospitalization overall. Notably, the early group had a higher body mass index (BMI) than the delayed group (20.7 vs. 16.9, p = 0.004). In addition, reopening occurred more frequently in the delayed group (1/9 vs. 5/8, p = 0.05). During spontaneous breathing trials, tidal volume (TV) and arterial oxygen tension were significantly higher in the early group compared to the delayed weaning group, but differences in RSBI and respiratory rate (RR) between groups were not statistically significant. CONCLUSIONS: Low BMI might be associated with delayed ventilator weaning in lung transplantation patients. In addition, instead of the traditional weaning predictors of RSBI and RR, TV might be a better predictor for ventilator weaning after lung transplantation.
Body Mass Index* ; Hospitalization ; Humans ; Intensive Care Units ; Lung Transplantation* ; Medical Records ; Oxygen ; Respiration ; Respiration, Artificial ; Respiratory Rate ; Retrospective Studies ; Tidal Volume ; Ventilator Weaning* ; Weaning

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs.
*Communicable Diseases, Emerging ; Humans ; *Immunity ; Research ; Systems Biology/*methods ; Vaccines/*immunology

Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components of both innate and adaptive immune systems experience aging-related changes, such as alterations in the number of circulating monocytic and dendritic cells, reduced phagocytic activities of neutrophils, limited diversity in B/T cell repertoire, T cell exhaustion or inflation, and chronic production of inflammatory cytokines known as inflammaging. The elderly are less likely to benefit from vaccinations as preventative measures against infectious diseases due to the inability of the immune system to mount a successful defense. Therefore, aging is thought to decrease the efficacy and effectiveness of vaccines, suggesting aging-associated decline in the immunogenicity induced by vaccination. In this review, we discuss aging-associated changes in the innate and adaptive immunity and the impact of immunosenescence on viral infection and immunity. We further explore recent advances in strategies to enhance the immunogenicity of vaccines in the elderly. Better understanding of the molecular mechanisms underlying immunosenescence-related immune dysfunction will provide a crucial insight into the development of effective elderly-targeted vaccines and immunotherapies.
Adaptive Immunity ; Aged ; Aging ; Communicable Diseases ; Cytokines ; Dendritic Cells ; Humans ; Immune System ; Immunosenescence ; Immunotherapy ; Inflation, Economic ; Neutrophils ; Vaccination ; Vaccines

BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.
Aging ; AMP-Activated Protein Kinases ; Animals ; Autophagy ; Blotting, Western ; Caenorhabditis elegans ; Cell Proliferation ; Fruit ; Gene Expression ; Hemagglutinins, Viral ; Humans ; Litchi ; Lung ; Lymphocytes ; Mice ; Orthomyxoviridae ; Phosphorylation ; Reactive Oxygen Species ; RNA, Messenger ; Spleen ; Superoxides ; Vibrio cholerae

Zika virus (ZIKV) is a member of Flaviviridae family that has emerged as a pathogen of significant public health importance. The rapid expansion of ZIKV in the South and Central America has recently gained medical attention emphasizing the capacity of ZIKV to spread to non-endemic regions. ZIKV infection during pregnancy has been demonstrated to cause microcephaly and other fetal developmental abnormalities. An increased incidence of Guillain-Barre syndrome, an immune mediated neuropathy of the peripheral nervous system, has also been reported in ZIKV-infected patients in French Polynesia and Brazil. No effective therapies currently exist for treating patients infected with ZIKV. Despite the relatively short time interval, an intensive effort by the global scientific community has resulted in development of animal models to study multiple aspects of ZIKV biology. Several animal models have been established to investigate pathogenesis of ZIKV in adults, pregnant mothers, and developing fetuses. Here we review the remarkable progress of newly developed small and large animal models for understanding ZIKV pathogenesis.
Adult ; Animals* ; Biology ; Brazil ; Central America ; Fetal Development ; Fetus ; Flaviviridae ; Guillain-Barre Syndrome ; Humans ; Incidence ; Microcephaly ; Models, Animal* ; Mothers ; Peripheral Nervous System ; Polynesia ; Pregnancy ; Public Health ; Zika Virus Infection* ; Zika Virus*

BACKGROUND: In March 2013, human infection with avian influenza A (H7N9) virus emerged in China, causing serious public health concerns and raising the possibility of avian-source pandemic influenza. Thus, the development of an effective vaccine for preventing and rapidly controlling avian influenza A (H7N9) virus is needed. In this study, we evaluated the immunogenicity of a synthetic DNA vaccine against H7 HA antigens in mice. MATERIALS AND METHODS: The synthetic consensus H7 HA DNA vaccine (25 or 50 µg) was administered to BALB/c mice at 0, 14, and 28 days by intramuscular injection followed by electroporation. Humoral and cellular immune responses were analyzed in a hemagglutination inhibition test and interferon-gamma enzyme-linked immunospot (ELISpot) assay, respectively. RESULTS: H7 HA-vaccinated mice showed 100% seroprotection and seroconversion rate against H7N9 reassortant influenza virus after both second and third immunizations. The geometric mean titer by the hemagglutination inhibition test increased with an increasing number of immunizations. However, there was no significant difference in geometric titer between the two groups injected with 25 and 50 µg of H7 HA DNA vaccine after two (79.98 vs. 107.65, P = 0.39) and three (159.96 vs. 215.28, P = 0.18) doses. In addition, the ELISpot assay revealed that administration of H7 HA DNA vaccine induced potent interferon-gamma production from mouse splenocytes. CONCLUSIONS: This study demonstrated the humoral and cellular immunogenicity of synthetic consensus H7 HA DNA vaccine in mice. This work demonstrates the potential of the H7 HA DNA vaccine as an efficient tool for the rapid control of emerging influenza A (H7N9) virus.
Animals ; China ; Consensus ; DNA* ; Electroporation ; Enzyme-Linked Immunospot Assay ; Hemagglutination Inhibition Tests ; Humans ; Immunity, Cellular ; Immunization ; Influenza in Birds* ; Influenza, Human ; Injections, Intramuscular ; Interferon-gamma ; Mice* ; Orthomyxoviridae ; Pandemics ; Public Health ; Seroconversion

BACKGROUND: Weaning from mechanical ventilation is difficult in the intensive care unit (ICU). Many controversial questions remain unanswered concerning the predictors of weaning failure. This study investigates patient characteristics and delayed weaning after lung transplantation. METHODS: This study retrospectively reviewed the medical records of 17 lung transplantation patients from October 2012 to December 2013. Patients able to be weaned from mechanical ventilation within 8 days after surgery were assigned to an early group (n = 9), and the rest of the patients were assigned to the delayed group (n=8). Patients' intraoperative and postoperative characteristics were collected and analyzed, and conventional weaning predictors, including rapid shallow breathing index (RSBI), were also assessed. RESULTS: The results of the early group showed a significantly shorter ICU stay in addition to a shorter hospitalization overall. Notably, the early group had a higher body mass index (BMI) than the delayed group (20.7 vs. 16.9, p = 0.004). In addition, reopening occurred more frequently in the delayed group (1/9 vs. 5/8, p = 0.05). During spontaneous breathing trials, tidal volume (TV) and arterial oxygen tension were significantly higher in the early group compared to the delayed weaning group, but differences in RSBI and respiratory rate (RR) between groups were not statistically significant. CONCLUSIONS: Low BMI might be associated with delayed ventilator weaning in lung transplantation patients. In addition, instead of the traditional weaning predictors of RSBI and RR, TV might be a better predictor for ventilator weaning after lung transplantation.
Body Mass Index ; Hospitalization ; Humans ; Intensive Care Units ; Lung Transplantation ; Medical Records ; Oxygen ; Respiration ; Respiration, Artificial ; Respiratory Rate ; Retrospective Studies ; Tidal Volume ; Ventilator Weaning ; Weaning