Toll-like receptor 5 （TLR5） signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89-96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. ...Toll-like receptor 5 （TLR5） signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89-96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. These observations indicate that the underlying mechanism remains incompletely understood. Here, we found that the native form of Salmonella typhimurium aa 89-96-mutant flagellin extracted from flagella retains some TLR5 recognition activity, indicating that aa 89-96 is the primary, but not the only site that imparts TLR5 activity. Additionally, this mutation impaired the production of IL-lp and IL-18. Using TLR5KO mice, we found that aa 89-96 is critical for the humoral adjuvant effect, but this effect was independent of TLR5 activation triggered by this region of flageUin. In summary, our findings suggest that aa 89-96 of flagellin is not only the crucial site responsible for TLR5 recognition, but is also important for humoral immune adjuvanticity through a TLR5-independent pathway.展开更多
The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capaci...The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres （IMHCSs） have an average particle size of -200 nm, large pore size of 15 rim, and high pore volume of 2.85 cmB.g-1. IMHCSs exhibited a very high loading capacity （1,040 ~tg-mg-1） towards ovalbumin （OVA, a model antigen）, controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 （Th2）-polarized response. Interferon-y and interleukin-4 concentration analysis revealed both T-helper 1 （Thl） and Th2 immune responses induced by OVA- loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.展开更多
OBJECTIVE: To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy. METHODS: Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy ...OBJECTIVE: To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy. METHODS: Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy were recruited in the study. All patients received monthly intramuscular injections of 3.75 mg triptorelin for three months prior to abdominal hysterectomy. RESULTS: There was significant reduction in the serum levels of oestradiol (68.6%), progesterone (95.6%) and luteinizing hormone (73.9%) and in uterine (45.0%) and fibroid (68.0%) volumes. The serum level of follicle-stimulating hormone and haemoglobin concentration were not significantly different. CONCLUSIONS: Shrinkage of uterine fibroids can be achieved in women who are rendered hypoestrogenic with monthly injections of triptorelin for three months. This treatment modality may be of value prior to hysterectomy or myomectomy especially when the fibroid is large.展开更多
Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile,...Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low im- munogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.展开更多
Background Keloids have a predilection for the aural region because of the special shape of the pinna. It is difficult to resect keloids entirely and maintain a satisfactory pinnal shape. Surgical excision in combinat...Background Keloids have a predilection for the aural region because of the special shape of the pinna. It is difficult to resect keloids entirely and maintain a satisfactory pinnal shape. Surgical excision in combination with radiotherapy is considered to be the most efficacious treatment available for severe keloids. This study was conducted to evaluate the treatment of aural keloids with intralesional excision and immediate postoperative adjuvant radiotherapy. Methods Forty-six patients with a combined total of 74 aural keloids were treated by intralesional excision and immediate postoperative adjuvant radiotherapy. All patients received a total dose of 20 Gy in 10 consecutive days. The time interval between keloid excision and delivery of the first radiotherapy fraction was 〈24 hours in all cases. The median follow-up was 2.2 years. Results Twenty-nine patients with 48 keloids （64.9%） were highly satisfied with their outcome, and were rated as good by the surgeon. Six patients with 12 keloids （16.2%） showed general satisfaction but wanted aesthetic refinement, and these patients were rated as fair by the surgeon. Three patients with four keloids （5.4%） showed no evidence of recurrence after surgery, but disliked the result because of the discoloration and irregularity of the scar surface. These patients were rated as poor by the surgeon. Partial recurrence occurred in 8 patients with 10 keloids （13.5%）. No major complications were observed. Conclusion Intralesional excision and immediate postoperative adjuvant radiotherapy is well tolerated and very effective in Dreventing recurrence of aural region keloids.展开更多
文摘Toll-like receptor 5 （TLR5） signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89-96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. These observations indicate that the underlying mechanism remains incompletely understood. Here, we found that the native form of Salmonella typhimurium aa 89-96-mutant flagellin extracted from flagella retains some TLR5 recognition activity, indicating that aa 89-96 is the primary, but not the only site that imparts TLR5 activity. Additionally, this mutation impaired the production of IL-lp and IL-18. Using TLR5KO mice, we found that aa 89-96 is critical for the humoral adjuvant effect, but this effect was independent of TLR5 activation triggered by this region of flageUin. In summary, our findings suggest that aa 89-96 of flagellin is not only the crucial site responsible for TLR5 recognition, but is also important for humoral immune adjuvanticity through a TLR5-independent pathway.
文摘The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres （IMHCSs） have an average particle size of -200 nm, large pore size of 15 rim, and high pore volume of 2.85 cmB.g-1. IMHCSs exhibited a very high loading capacity （1,040 ~tg-mg-1） towards ovalbumin （OVA, a model antigen）, controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 （Th2）-polarized response. Interferon-y and interleukin-4 concentration analysis revealed both T-helper 1 （Thl） and Th2 immune responses induced by OVA- loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.
文摘OBJECTIVE: To study the effects of pretreatment with triptorelin on uterine fibroid before abdominal hysterectomy. METHODS: Fifteen premenopausal Chinese women with symptomatic uterine fibroids requiring hysterectomy were recruited in the study. All patients received monthly intramuscular injections of 3.75 mg triptorelin for three months prior to abdominal hysterectomy. RESULTS: There was significant reduction in the serum levels of oestradiol (68.6%), progesterone (95.6%) and luteinizing hormone (73.9%) and in uterine (45.0%) and fibroid (68.0%) volumes. The serum level of follicle-stimulating hormone and haemoglobin concentration were not significantly different. CONCLUSIONS: Shrinkage of uterine fibroids can be achieved in women who are rendered hypoestrogenic with monthly injections of triptorelin for three months. This treatment modality may be of value prior to hysterectomy or myomectomy especially when the fibroid is large.
文摘Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low im- munogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.
文摘Background Keloids have a predilection for the aural region because of the special shape of the pinna. It is difficult to resect keloids entirely and maintain a satisfactory pinnal shape. Surgical excision in combination with radiotherapy is considered to be the most efficacious treatment available for severe keloids. This study was conducted to evaluate the treatment of aural keloids with intralesional excision and immediate postoperative adjuvant radiotherapy. Methods Forty-six patients with a combined total of 74 aural keloids were treated by intralesional excision and immediate postoperative adjuvant radiotherapy. All patients received a total dose of 20 Gy in 10 consecutive days. The time interval between keloid excision and delivery of the first radiotherapy fraction was 〈24 hours in all cases. The median follow-up was 2.2 years. Results Twenty-nine patients with 48 keloids （64.9%） were highly satisfied with their outcome, and were rated as good by the surgeon. Six patients with 12 keloids （16.2%） showed general satisfaction but wanted aesthetic refinement, and these patients were rated as fair by the surgeon. Three patients with four keloids （5.4%） showed no evidence of recurrence after surgery, but disliked the result because of the discoloration and irregularity of the scar surface. These patients were rated as poor by the surgeon. Partial recurrence occurred in 8 patients with 10 keloids （13.5%）. No major complications were observed. Conclusion Intralesional excision and immediate postoperative adjuvant radiotherapy is well tolerated and very effective in Dreventing recurrence of aural region keloids.
