1.The changes of serum nerve growth factor and interleukin-15 in children with mycoplasma pneumoniae pneumonia and its clinical significance
Caixia LU ; Chun'e LI ; Jun LI ; Zezhong YAO ;
Chinese Pediatric Emergency Medicine 2014;21(1):31-33
Objective To investigate the changes of serum nerve growth factor(NGF) and interleukin(IL)-15 levels in children with mycoplasma pneumoniae pneumonia(MPP) and its clinical significance.Methods Using the antibody sandwich ELISA method to measure the serum NGF and IL-15 levels in 65 cases of MPP (MPP group,which contains two groups:the severe group contains 25 patients and the mild group contains 40 patients) and 50 cases of healthy children (normal control group).Results The serum NGF,IL-15 levels in the acute phase of MPP group were (157.62 ± 33.45) pg/ml and (242.51 ± 60.04) pg/ml,and in the recovery period were (99.58 ±21.29) pg/ml and (145.90 ±50.25) pg/ml,they were all significantly higher than the normal control group [(29.86-± 11.74) pg/ml and (108.86 ± 21.14) pg/ml,P < 0.05].The serum NGF,IL-15 of the acute phase were also higher than the recovery period (P <0.05).In the acute phase of MPP,serum NGF,IL-15 levels in the severe group were significantly higher than in the mild group [(204.38±27.52) pg/ml vs (128.39 ±22.07) pg/ml,(288.58 ±55.33) pg/ml vs (213.71 ±42.69) pg/ml],and the differences were statistically significant (P < 0.05) ; in the recovery period of MPP group,the serum NGF,IL-15 levels of severe group were higher than the mild group,but the difference was not statistically significant (P >0.05).Conclusion The serum levels of NGF,IL-15 in the mycoplasma pneumoniae infection patients are significantly increased,and they are all decreased as the disease mitigation.It is prompted that NGF and IL-15 participate in the pathogenesis of infection by mycoplasma pneumoniae.
2.Community-based Rehabilitation on Disabled Affected by Leprosy
Lianhua ZHANG ; Weiguo XU ; Hongjun WANG ; Zezhong LU
Chinese Journal of Rehabilitation Theory and Practice 2008;14(2):196-197
Objective To explore the manner of the community-based rehabilitation(CBR)on the disabled affected by leprosy(DAL).Methods Two towns with more DALs were selected as pilot areas to set up a station for CBR in township hospital respectively.Under the leadership of governments on local county and township levels and using the health resources of township hospital recovery service was offered freely to DALs periodically.Certainly,the DALs were willing to participate the program,the township hospital and doctors offered service should be paid by local county health bureau.Results The station for CBR had run in right path and its range of service expanded around the 2 towns.Most part of DALs had cured or distinctly improved their exposure conjunctivitis,cracks of in numb hands and feet,foot ulcers.The style of the station for CBR had been accepted by local people and DALs.Finally,the township hospital and doctor offered service also earned from the station for CBR service.Conclusion CBR should be the most important part of leprosy rehabilitation.The general health services offering the rehabilitation of leprosy work is feasible,which only need pay a little.It also reflects and deepens the strategy advocated by WHO on the sustainability of Leprosy Control Program.
3.A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.
Jie ZHOU ; Wei XU ; Zezhong LIU ; Chao WANG ; Shuai XIA ; Qiaoshuai LAN ; Yanxing CAI ; Shan SU ; Jing PU ; Lixiao XING ; Youhua XIE ; Lu LU ; Shibo JIANG ; Qian WANG
Acta Pharmaceutica Sinica B 2022;12(4):1652-1661
The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.
4.An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.
Zezhong LIU ; Wei XU ; Zhenguo CHEN ; Wangjun FU ; Wuqiang ZHAN ; Yidan GAO ; Jie ZHOU ; Yunjiao ZHOU ; Jianbo WU ; Qian WANG ; Xiang ZHANG ; Aihua HAO ; Wei WU ; Qianqian ZHANG ; Yaming LI ; Kaiyue FAN ; Ruihong CHEN ; Qiaochu JIANG ; Christian T MAYER ; Till SCHOOFS ; Youhua XIE ; Shibo JIANG ; Yumei WEN ; Zhenghong YUAN ; Kang WANG ; Lu LU ; Lei SUN ; Qiao WANG
Protein & Cell 2022;13(9):655-675
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2
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Antibodies, Neutralizing
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Antibodies, Viral
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COVID-19
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Epitopes
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Humans
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SARS-CoV-2/genetics*
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Spike Glycoprotein, Coronavirus/genetics*