INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Donghui Li,Wenbo Li,Sheng Li,Yangyang Zhang,Xianwen Hu,Shilin Liu,Yan Li
Nasal vaccine is a non-invasive vaccine that activates systemic and mucosal immunity in the presence of an adjuvant, thereby enhancing immune function. In this work, chitosan/oligochitosan/tween 80 (CS-COS-T80) co-stabilized emulsion was designed and further used as the nasal adjuvant. CS-COS-T80 emulsion exhibited outstanding stability under pH 6–8 with uniformly dispersed droplets and nano-scale particle size (<0.25 μm), and maintained stable at 4 °C for 150-day storage. Addition of model antigen ovalbumin (OVA) had no effect on the stability of CS-COS-T80 emulsion. In vivo nasal immunity indicated that CS-COS-T80 emulsion prolonged the retention time of OVA in the nasal cavity (from 4 to 8 h to >12 h), as compared to T80-emulsion. CS-COS-T80 emulsion produced a stronger mucosal immune response to OVA, with secretory IgA levels 5-fold and 2-fold higher than those of bare OVA and commercial adjuvant MF59, respectively. Compared to MF59, CS-COS-T80 induced a stronger humoral immune response and a mixed Th1/Th2 immune response of OVA after immunization. Furthermore, in the presence of CS-COS-T80 emulsion, the secretion of IL-4 and IFN-γ and the activation of splenocyte memory T-cell differentiation increased from 173.98 to 210.21 pg/mL and from 75.46 to 104.01 pg/mL, respectively. Therefore, CS-COS-T80 emulsion may serve as a promising adjuvant platform.
研究领域:
药学
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免疫学
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生物技术
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shaoyang Zhi,Junli Wang,Yiran Wang,Yijie Li,Mengjuan Zhao,Liping Yang,Chaobin Qin,Xiao Yan,Guoxing Nie
AMPKα1 and AMPKα2, key kinases in regulating energy homeostasis, have not been previously cloned or characterized in common carp ( Cyprinus carpio ). This study identified the open reading frame (ORF) sequences of ampkα1 (1722 bp, encoding 573 amino acids) and ampkα2 (1659 bp, encoding 552 amino acids) through homologous cloning. Sequence alignment and phylogenetic analysis showed a high similarity of both genes with fish homologs. Expression analysis revealed that ampkα1 and ampkα2 are widely expressed across tissues in carp, with ampkα1 highly expressed in the gonads and ampkα2 in the heart. Fasting significantly reduced ampkα1 expression in the heart, adipose tissue, and foregut but increased it in the hindgut and white muscle. Similarly, ampkα2 expression decreased in the hypothalamus and muscle during fasting, with an increase in the midgut. Glucose tolerance tests showed dynamic regulation of ampkα1 and ampkα2 , with initial downregulation followed by upregulation in the hepatopancreas, red muscle, and brain. High-glucose and high-fat diets significantly increased ampkα1 and ampkα2 expression in multiple tissues. Insulin and glucagon treatment induced time-dependent changes in both genes in hepatocytes, while Aeromonas hydrophila infection, LPS, and Poly (I:C) stimulation upregulated ampkα1 and ampkα2 in immune-related tissues. Knockdown of ampkα2 , but not ampkα1 , reduced glut1b mRNA levels, while both knockdowns of ampkα1 and ampkα2 promoted the expression of gsk3β , pygm , acc , fas , srebp , cs , and pro-inflammatory cytokines, suggesting their involvement in metabolic and immune regulation in carp.
研究领域:
分子生物学
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营养学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Pathogens
·
2021
·Vol. 11
·期 1
·7
·
IF 3.492
Fuchun Zhang,Lingling Sun,Mark K. Lafferty,Joseph B. Margolick,Alfredo Garzino-Demo
CD4+CCR6+T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6+T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are few existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin,Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.Keywords:CCR6;MIP-3α;immune response;antigen stimulation;Th17
研究领域:
免疫学
·
病毒学
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DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Wenjiao Fu,Mengyu Guo,Xuemei Zhou,Zhenzhen Wang,Jiufeng Sun,Yaling An,Tong Guan,Mingdi Hu,Jiayang Li,Ziwei Chen,Jinmin Ye,Xingfa Gao,George Fu Gao,Lianpan Dai,Yaling Wang,Chunying Chen
Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol–gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a “mucosal mask”. The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.
研究领域:
病毒学
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免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Anan Guo,Lvqing Tang,Bing Yang,Niling Xie,Yandong Cui,Wen Sun,Yuan Li,Xiangting Li,Yang Wu,Yingshuai Liu
Adjuvants including aluminum adjuvant (Alum) and oil-water emulsion have been widely used in inactivated pseudorabies virus (PRV) vaccines to improve their performance, however, they are not sufficient to protect from PRV infection because of the weak immune response and poor Th1-type immune response. Divalent manganese ion (Mn 2+ ) has been reported to increase the cellular immune response significantly. In this work, a xanthan gum and carbomer-dispersed Mn 2+ -loaded tannic acid-polyethylene glycol (TPMnXC) nanoparticle colloid is developed and used as an adjuvant to improve the performance of the inactivated PRV vaccine. The good in vitro and in vivo biocompatibility of the developed TPMnXC colloid has been confirmed by the cell viability assay, erythrocyte hemolysis, blood routine analysis, and histological analysis of mouse organs and injection site. The TPMnXC-adjuvanted inactivated PRV vaccine (TPMnXC@PRV) significantly promotes higher and more balanced immune responses indicating with an increased specific total IgG antibody and IgG2a/IgG1 ratio, efficient splenocytes proliferation, and elevated Th1- and Th2-type cytokine secretion than those of control groups. Wild PRV challenge experiment is performed using mice as a model animal, achieving a protection rate of up to 86.67 %, which is much higher than those observed from the commercial Alum. This work not only demonstrates the high potentiality of TPMnXC in practical applications but also provides a new way to develop the Mn 2+ -loaded nanoadjuvant for veterinary vaccines.
研究领域:
兽医学
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免疫学
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纳米技术
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病毒学
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产品关联
DOI
PubMed
高影响因子
BULLETIN OF ENTOMOLOGICAL RESEARCH
·
2018
·Vol. 109
·期 2
·248-256
·
IF 1.721
E. Meng,J. Li,B. Tang,Y. Hu,T. Qiao,Y. Hou,Y. Lin,J. Li,Z. Chen
Although parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.
研究领域:
昆虫学
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免疫学
·
微生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jianchen Zhang,Yu Liu,Ying Guan,Yongjun Zhang
Prophylactic human papillomavirus (HPV) vaccines against cervical cancer were successfully developed; however, challenges such as high cost and low compliance still remain to be overcome. In addition, because many HPV types can cause cervical cancer, antigens of multiple HPV types are needed to achieve broad protection. In this study, a bivalent single-injection HPV vaccine was designed in which virus-like particles (VLPs) of HPV 16 L1 and HPV 18 L1 were used as antigens. A recently developed drug carrier that uses tannic acid/polyethylene glycol films as the erodible layer was employed to accomplish multiple pulsatile releases of the antigens. Monovalent single-injection vaccines for HPV 16 and HPV 18 were first designed. A bivalent single-injection vaccine was then obtained by simply mixing the two monovalent vaccines. The bivalent vaccine provided protection against both HPV types. More importantly, it elicited both humoral and cellular immune responses as potent as those elicited by the corresponding multiple dose vaccine because of their similar release profile of antigens. Cross-reactivity was observed between HPV 16 and 18 in terms of cellular immune responses, while no cross-reactivity was found in terms of humoral immune responses. Note that other multivalent single-injection vaccines could be designed in the same way. These vaccines are expected to help prevent cervical cancer because of their broad protection, enhanced compliance and lowered vaccination cost.
研究领域:
免疫学
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病毒学
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药学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
VACCINE
·
2023
·
IF 5.5
Shuwen Xu,Zhiyong Wu,Gaofeng Cai,Yue Zhang,Song Peng,Lina Jiao,Zhenguang Liu,Yang Yang,Deyun Wang
Oil-in-water emulsion-based adjuvants have demonstrated acceptable safety in many disease indications, while their adjuvant activities for vaccines still need to be improved. Recently, the strategy of combining adjuvants with multiple types of immunostimulants has been shown to enhance immune responses. In this study, astragalus polysaccharides were combined with simvastatin as an immunostimulant to construct a compound O/W emulsion adjuvant. The formulations were optimized according to the OVA-specific antibody responses induced in mice. For this reason, high (5 mg/mL), medium (2.5 mg/mL), and low (1.25 mg/mL) concentrations of astragalus polysaccharides and high (10 mg/mL), medium (1 mg/mL), and low (0.1 mg/mL) concentrations of simvastatin were selected. The final optimal formulation of the immunostimulant was a high concentration of astragalus polysaccharides combined with a medium concentration of simvastatin. The optimal compound O/W emulsion adjuvant could induce effective humoral and cellular immune responses that were stronger and more stable than those induced by aluminum adjuvant and Freund's adjuvant. The OVA/HAPS-MSim-OE induced dramatically strong and persistent IgG expressions and Th1-polarized immune responses. What’s more, the highest CD4 + /CD8 + lymphocyte ratios were observed in OVA/HAPS-MSim-OE group. In addition, compound O/W emulsion adjuvant groups significantly promoted the secretion of IFN-γ and IL-6, which also indicated that the compound O/W emulsion adjuvants could induce both enhanced Th1 and Th2-mediated immune responses but prefer the Th1-mediated ones. This study would contribute to an interesting and promising direction in the development of emulsion-based adjuvants.
研究领域:
免疫学
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药学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Panpan Xue,Huilan Zhuang,Sijie Shao,Hai Cai,Shumin Tang,Ying Sun,Xuemei Zeng,Shuangqian Yan
Abnormal copper and iron ion metabolism promotes tumor proliferation but also presents a potential target for cancer therapy. However, simultaneously modulating these two ions is challenging, and the downstream therapeutic mechanisms remain unexplored. Here, we introduce Fe ss TMiR, a biodegradable ionic nanoregulator designed to modulate copper and iron ion homeostasis for tumor treatment. Fe ss TMiR comprises ferrous ions and disulfanediyldiacetic acid-assembled nanovectors (Fe ss NV) combined with tetrathiomolybdate (TM), an anti-copper agent. Under the acidic and high-glutathione conditions of the tumor microenvironment, Fe ss TMiR decomposes into ferrous ions and TM, leading to elevated iron and reduced copper levels. Transcriptome analysis reveals that this dual ion modulation induces cancer cell death via ferroptosis, apoptosis, and autophagy by affecting multiple pathways, including metal ion metabolism, glutathione metabolism, and oxidative stress. Additionally, Fe ss TMiR inhibits angiogenesis and reduces the expression of programmed cell death ligand 1 (PD-L1). Notably, Fe ss TMiR elicits robust antitumor immune responses in breast tumor mouse models, including dendritic cell maturation, Treg cell reduction, and enhanced T cell tumor infiltration. This study underscores the potential of modulating iron and copper homeostasis in tumor therapy, enhancement of antitumor immune responses, and activation of ferroptosis.
研究领域:
肿瘤学
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生物化学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
PLANT CELL REPORTS
·
2025
·Vol. 44
·期 2
·1-15
·
IF 4.5
Li Xue,Zhou Yue,Chen Hang,Guo Zetian,Zhang Jinlian,Chen Wenli
Key message The three SDEs of C Las were expressed in citrus leaves by AuNPs-PEI mediated transient expression system, and promoted the proliferation of C Las and inhibited citrus immunity. Huanglongbing (HLB) is the most severe bacterial disease of citrus caused by Candidatus Liberibacter asiaticus ( C Las). C Las suppress host immune responses and promote infection by sec-dependent effectors (SDEs), thus insight into HLB pathogenesis is urgently needed to develop effective management strategies. In this study, we focused on the roles of SDE4310 , SDE4435 and SDE4955 in citrus. We found that the expression of SDE4310 , SDE4435 and SDE4955 to increase with increasing citrus immune genes CsPR1 , CsPR2 , CsPR5 , CsNPR1 , CsRBOHD , CsMAP3K and CsBIK1 , suggesting that the level of citrus immunity could be judged by the expression of SDE. To further explore the relationship between these three SDEs and citrus immunity, we established a transient expression system in citrus leaves, using gold nanoparticle-polyethyleneimine (AuNPs-PEI) to deliver recombinant plasmid containing SDE4310 , SDE4435 or SDE4955 respectively into citrus leaves. Results showed that SDE4310 , SDE4435 and SDE4955 were successfully expressed in citrus leaves using this transient expression system, and found that SDE4310 , SDE4435 and SDE4955 could promote the C Las proliferation by decreasing the immune gene expression of the citrus. Additionally, we used AuNPs-PEI to deliver siRNA 4310 to citrus cells, significantly reducing the expression of SDE4310 within 3 days. Although the suppression of SDE4310 expression did not inhibit the C Las proliferation, it increased the expression level of CsPR1 , CsNPR1 and CsBIK1 . This is also the first time that AuNPs-PEI has been found to be able to deliver exogenous plasmids into citrus cells and express the target protein, providing a new method for future studies on citrus HLB.
研究领域:
植物病理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Saifei Liu,Muye Xiao,Anfei Fang,Binnian Tian,Yang Yu,Chaowei Bi,Dongfang Ma,Yuheng Yang
Plant lysin motif (LysM) ectodomain receptors interact with pathogen-associated molecular patterns (PAMPs) and have critical functions in plant–microbe interactions. In this study, 65 LysM family genes were identified using the recent version of the reference sequence of bread wheat (Triticum aestivum), in which 23, 16, 20, and 6 members belonged to LysM-containing receptor-like kinases (LYKs), LysM-containing receptor-like proteins (LYPs), extracellular LysM proteins (LysMes), and intracellular nonsecretory LysM proteins (LysMns), respectively. The study found that TaCEBiP, TaLYK5, and TaCERK1 were highly responsive to PAMP elicitors and phytopathogens, with TaCEBiP and TaLYK5 binding directly to chitin. TaCERK1 acted as a coreceptor with TaCEBiP and TaLYK5 at the plasma membrane. Overexpression of TaCEBiP, TaLYK5, and TaCERK1 in Nicotiana benthamiana leaves exhibited enhanced resistance to Sclerotinia sclerotiorum. Subsequently, knocking down TaCEBiP, TaLYK5, and TaCERK1 genes with barley stripe mosaic virus–VIGS compromised the wheat defense response to an avirulent strain of Puccinia striiformis. The study concluded that wheat has two synergistic chitin perception systems for detecting pathogen elicitors, with the activated CERK1 intracellular kinase domain leading to signaling transduction. This research provides valuable insights into the functional roles and regulatory mechanisms of wheat LysM members under biotic stress.
研究领域:
植物学
·
分子生物学
·
植物病理学
✓ 已验证
DOI
高影响因子
Plants-Basel
·
2025
·Vol. 14
·期 8
·1243
·
IF 4.1
Xiao Wang,Qian Tan,Xiyue Bao,Xinyue Gong,Lingmin Zhao,Jieyin Chen,Lei Liu,Ran Li
Tomatoes are important horticultural crops worldwide. Verticillium wilt is a disease caused byVerticillium dahliaethat causes serious tomato yield losses.V. dahliaecan be classified into three distinct races in tomatoes. We identified the specificVdR3egene ofV. dahliaerace 3 and found that VdR3e triggered immune responses in the resistant tomato cultivar IVF6384. We confirmed that VdR3e triggers immune responses in the parents of IVF6384 plants and conducted transcriptome sequencing between male and female IVF6384 plants after VdR3e infiltration to analyze the potential regulatory network response to VdR3e. We found that both parents had a series of detoxification and stress resistance responses to VdR3e, but those of the male IVF6384 parent were concentrated in disease resistance-related signaling pathways. Moreover, several vital differentially expressed genes involved in functional annotation related to plant–pathogen interactions and plant hormone signaling stimulated immune responses inNicotiana benthamiana. This study provides a new and comprehensive perspective on tomato resistance to Verticillium wilt.
研究领域:
植物学
·
遗传学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）