Gamma-Irradiated Non-Capsule Group B Streptococcus Promotes T-Cell Dependent Immunity and Provides a Cross-Protective Reaction

Group B Streptococcus (GBS) is a Gram-positive bacterium commonly found in the genitourinary tract and is also a leading cause of neonatal sepsis and pneumonia. Despite the current antibiotic prophylaxis (IAP), the disease burdens of late-onset disease in newborns and non-pregnant adult infections are increasing. Recently, inactivation of the pathogens via gamma radiation has been proven to eliminate their replication ability but cause less damage to the antigenicity of the key epitopes. In this study, the non-capsule GBS strain was inactivated via radiation (Rad-GBS) or formalin (Che-GBS), and we further determined its immunogenicity and protective efficacy as vaccines. Notably, Rad-GBS was more immunogenic and gave rise to higher expression of costimulatory molecules in BMDCs in comparison with Che-GBS. Flow cytometric analysis revealed that Rad-GBS induced a stronger CD4+ IFN-γ+ and CD4+IL-17A+ population in mice. The protective efficacy was measured through challenge with the highly virulent strain CNCTC 10/84, and the adoptive transfer results further showed that the protective role is reversed by functionally neutralizing antibodies and T cells. Finally, cross-protection against challenges with prevalent serotypes of GBS was induced by Rad-GBS. The higher opsonophagocytic killing activity of sera against multiple serotypes was determined in sera from mice immunized with Rad-GBS. Overall, our results showed that the inactivated whole-cell encapsulated GBS could be an alternative strategy for universal vaccine development against invasive GBS infections

Anti-inflammatory properties of extracts from Chimonanthus nitens Oliv. leaf.

Chimonanthus nitens Oliv. (CN) is a species in the family Calycanthaceae. Its leaf is widely used to make traditional herbal tea in southern China and has a wide range of therapeutic effects. The profile of the ethanol extracts from CN leaves was identified by UPLC-QTOF-MS/MS. Forty seven compounds were determined including organic acids, phenolic acids and derivatives, flavonoids, coumarins, fatty acids and other compounds. The effect of the CN extracts on the inflammatory damage in zebrafish and in RAW 264.7 cells was investigated. The extracts demonstrated a strong ability to inhibit the recruitment of neutrophils in LPS-stimulated zebrafish, but macrophage migration was not significantly affected. Pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1β) were also determined by q-PCR. The extracts strongly reduced mRNA expression of TNF-α, IL-6 but not IL-1β in zebrafish model, while significantly inhibited the production of the factors in the RAW 264.7 cells. Therefore, our results suggest that the ethanol extracts of CN leaves may serve as a source of nutraceutical compounds with anti-inflammatory properties

CD30 Is Highly Expressed in Chronic Obstructive Pulmonary Disease and Induces the Pulmonary Vascular Remodeling

Chronic obstructive pulmonary disease (COPD) is one of the common and underdiagnosed diseases with the highest morbidity and mortality in the world. The development of COPD can lead to pulmonary vascular remodeling and pulmonary hypertension, further causing the occurrence of pulmonary heart disease. Therefore, attenuation of pulmonary vascular remodeling and pulmonary hypertension caused by COPD can significantly delay cardiovascular complications. In the study, we firstly found that the expression of CD30 and CD30L was increased in COPD. Importantly, the serum CD30L levels were significantly higher in patients with stable COPD relative to those with acute exacerbation of COPD (AECOPD). This suggested that CD30 might be related to the development of COPD. In addition, we found that the expression of CD30 in the COPD rat model was significantly increased compared with control group. And treatment with the anti-CD30 antibody reduced the serum concentration and tissue expression of CD30 in rat. Importantly, anti-CD30 antibody alleviated pulmonary vascular remodeling in COPD model rats. This suggested that CD30 played an important role in the course of COPD. Finally, we found that, in the HPASMC and HPAEC cell lines, CD30 can affect the cell viability and cell migration and inhibited hypoxia-induced cell apoptosis in a concentration-dependent manner. We also found CD30 induced extracellular matrix formation through decreasing the expression of MMP-2, thus promoting the pulmonary vascular remodeling. The study indicated that CD30 and CD30L were involved in pulmonary vascular remodeling and inflammatory response in COPD. Altogether, CD30 might be a marker for the early diagnosis and progression of COPD

Inhibitory effect of CN leaf extracts on the production of pro-inflammatory cytokines in zebrafish (A) or RAW 264.7 macrophages (B, C, D).

<p>Data were shown as mean ± S.E. (n = 3). * indicates p<0.05, ** is p<0.01, *** is p<0.001.</p

Anti-inflammatory properties of extracts from <i>Chimonanthus nitens</i> Oliv. leaf - Fig 1

<p>A. DAD chromatogram at 360 nm of <i>Chimonanthus nitens</i> Oliv. leaves extracts; B. Total ion chromatogram (TIC) of CN extracts in negative ion mode.</p

Macrophages and neutrophils migrated to the injured area were count.

<p><b>A-F, images show the macrophages and neutrophils migrated to the yolk microinjected by LPS at 6 hpi. G, neutrophils count in yolk at 6 hpi (n = 20). H and I, microinjection site were marked by * and cell count area were marked by red circle. J-O, images show the macrophages and neutrophils migrated to the somite muscle microinjected by LPS at 6 hpi. P, macrophages and neutrophils count in somite muscle at 6 hpi (n = 11).</b> Data were shown as mean ± S.E. For G and P, * indicates p<0.05, ** is p<0.01, *** is p<0.001.</p

The effect of CN extract on mRNA expression of TNF-α, IL-6 and IL-1β.

<p>Data were shown as mean ± S.E. (n = 3). * indicates p<0.05, ** is p<0.01, *** is p<0.001.</p

The effect of CN extract on cell viability.

<p>Data were shown as mean ± S.E. (n = 3). * indicates p<0.05, ** is p<0.01, *** is p<0.001.</p

Identification of compounds in <i>Chimonanthus nitens</i> leaves Oliv. by UPLC -QTOF-MS/MS.

<p>Identification of compounds in <i>Chimonanthus nitens</i> leaves Oliv. by UPLC -QTOF-MS/MS.</p

The total flavonoid contents (TFC) and individual compound contents of <i>Chimonanthus nitens</i> Oliv. leaves.

<p>The total flavonoid contents (TFC) and individual compound contents of <i>Chimonanthus nitens</i> Oliv. leaves.</p