Pulmonary surfactant is a complex and highly surface-active material. It covers the alveolar epithelium and consists of 90% lipids and 10% proteins. Pulmonary surfactant lipids together with pulmonary surfactant proteins facilitate breathing by reducing surface tension of the air-water interface within the lungs, thereby preventing alveolar collapse and the mechanical work required to breathe. Moreover, pulmonary surfactant lipids, such as phosphatidylglycerol and phosphatidylinositol, and pulmonary surfactant proteins, such as surfactant protein A and D, participate in the pulmonary host defense and modify immune responses. Emerging data have shown that pulmonary surfactant lipids modulate the inflammatory response and antiviral effects in some respiratory viral infections, and pulmonary surfactant lipids have shown promise for therapeutic applications in some respiratory viral infections. Here, we briefly review the composition, antiviral properties, and potential therapeutic applications of pulmonary surfactant lipids in respiratory viral infections.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-c production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8 1 T cells from immunized animals, antigen-specific CD8 1 T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients. Cellular & Molecular Immunology
Objectives: To compare the clinical efficacy of a new retractor-assisted Wiltse transforaminal lumbar interbody fusion (TLIF), minimally invasive TLIF (MIS-TLIF), and traditional posterior lumbar interbody fusion (PLIF) in treating single-level lumbar degenerative diseases.Methods: A retrospective study was conducted by analyzing the clinical and imaging data of consecutive patients with single-level lumbar degenerative diseases who underwent the new retractor-assisted Wiltse TLIF, MIS-TLIF, or traditional PLIF. This study enrolled 87 concurrent patients between June 2016 and December 2019 (Wiltse TLIF 29 cases; MIS-TLIF 28 cases; PLIF 30 cases). The three groups were compared for perioperative indicators (including intraoperative blood loss, postoperative drainage volume, operation time, intraoperative fluoroscopy time, bedridden time), creatine kinase (CK), visual analog score (VAS), Oswestry disability index (ODI), Japanese Orthopaedic Association (JOA) score, intervertebral fusion rate, muscle atrophy, and fatty infiltration (including ratio of multifidus atrophy and ratio of lean-to-total cross-sectional area [CSA]).Results: Intraoperative blood loss (F = 62.628, p < 0.001), postoperative drainage volume (F = 72.048, p < 0.001), and bedridden time (χ 2 = 62.289, p < 0.001) were significantly lower in the MIS-TLIF and Wiltse groups than in the PLIF group. The operative and intraoperative radiation times of the MIS-TLIF group were significantly longer than those of the Wiltse and PLIF groups. The CK concentration in the Wiltse and MIS-TLIF groups were significantly lower than those in the PLIF group 1 day (F = 9.331, p < 0.001) and 3 days after surgery (F = 15.967, p < 0.001). The PLIF group's back pain VAS score was higher than those of the Wiltse and MIS-TLIF groups. The PLIF group had a higher ODI 6 months (F = 3.282, p = 0.042) and 12 months (F = 5.316, p = 0.007) after surgery and a lower JOA score than the Wiltse and MIS-TLIF groups 6 months (F = 3.234, p = 0.044) and 12 months (F = 3.874, p = 0.025) after surgery. The ratio of multifidus atrophy in the PLIF group (41.70 AE 8.84%) was significantly higher than those of the Wiltse group (24.13 AE 6.82%) and the MIS-TLIF group (22.35 AE 5.03%). The ratio of lean-to-total CSA in the PLIF group was lower than those of the Wiltse and MIS-TLIF groups after surgery (F = 8.852, p < 0.001). MIS-TLIF group showed longer operation time (169.11 AE 29.38 min) and intraoperative fluoroscopy time (87.61 AE 3.13 s) than the Wiltse group. Conclusion:Wiltse TLIF assisted by the new retractor is a more convenient and minimally invasive surgical method than the traditional PLIF and MIS-TLIF methods, which are linked to a long learning curve and long operation and fluoroscopy time.
An HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4 T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8 T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4 and CD8 T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-β and Foxp3) in CD4 T cells. In the alum immunized group, slight increase of IL-10, TGF-β and Foxp3 in CD4 T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.
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