MOLECULAR HUMAN REPRODUCTION
·
2021
·Vol. 27
·期 11
·
IF 4.025
Guo Fang,He Yongpei,Fan Yixian,Du Zhenzhen,Sun Huanhuan,Feng Zuohua,Zhang Guimei,Xiong Ting
Evidence accumulated in recent years has revealed that neutrophils are involved in the initial establishment of endometriosis, which is well-known as a chronic inflammatory disease. So far, why and how neutrophils promote the formation of early endometriosis are still unclear. In this study, using a mouse model of endometriosis, we demonstrated that endometriosis mice (EMs mice) had a significantly increased number of neutrophils in peritoneal fluids and lesions, and increased levels of granulocyte colony-stimulating factor (G-CSF) and IL-6 in serum and peritoneal fluids compared to the control group. In the neutrophils and uterine fragments co-injection experiment, neutrophils regulated by G-CSF and IL-6 had a similar effect to neutrophils from EMs mice, increasing the number, area, weight and microvessel density (MVD) of endometriotic lesions. Blocking the effect of G-CSF and IL-6 in EMs mice resulted in a decrease in the number, area and weight of endometriotic lesions. Following the depletion of neutrophils in vivo using a anti-Ly6G antibody, the MVD in the lesions of mice treated with neutrophils from EMs mice and neutrophils from pG/pI6 mice were significantly reduced. Neutrophils from EMs mice and neutrophils from pG/pI6 mice altered the expression levels of Mmp9, Bv8 and Trail genes compared to the neutrophils from PBS-treated mice. IL-6 together with G-CSF induced a higher expression of phospho-STAT3 and STAT3 in neutrophils. These findings suggest that neutrophils modulated by G-CSF and IL-6 through the STAT3 pathway alter the expression levels of the angiogenesis-related genes Mmp9, Bv8 and Trail, and may promote the establishment of early endometriosis.
研究领域:
免疫学
·
生殖医学
·
炎症
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·376
·
IF 5.5
Yuxing Zhang,Xixi Zou,Qiran Du,Xiaotao Dong,Uday Kumar Chinta,Ruyue Yu,Fei Wu,Tuo Jin
Objectives: Thermo-gelling hydrophilic polymers like PLGA–PEG–PLGA are known as injectable sustained-release depots for biologics, but they face challenges due to the occurrence of severe burst release. This study aimed to develop a strategy to avoid the initial burst release by pre-encapsulating proteins in polysaccharide microparticles through an aqueous–aqueous emulsion mechanism, thereby enhancing therapeutic retention and linear release kinetics.Methods: Five model proteins (G-CSF, GM-CSF, IGF-1, FVIII, BSA) were encapsulated in dextran microparticles, using an organic solvent-free aqueous–aqueous emulsion method. These particles were dispersed in a 23% (w/w) PLGA–PEG–PLGA solution and injected into a 37 °C release buffer to form a gel depot. The in vitro release profiles were quantified using ELISA and MicroBCA assays over 9–42 days. The bioactivity of the proteins was validated using cell proliferation assays (NFS-60, TF-1, MCF-7) and chromogenic kits. The in vivo pharmacokinetics of the FVIII-loaded formulations were evaluated in Sprague–Dawley rats (n = 5/group) over 28 days.Results: Protein-loaded dextran particles retained their structural integrity within the hydrogel and exhibited minimal burst release (≤5% within 30 min vs. >25% for free proteins). Sustained near-linear release profiles were observed for all the proteins, with complete release by day 9 (G-CSF, GM-CSF, BSA) or day 42 (FVIII). Rats administered with the thermal gel with FVIII–dextran particles showed a significantly lower peak plasma concentration (Cmax: 88.25 ± 30.21 vs. 132.63 ± 66.67 ng/mL) and prolonged therapeutic coverage (>18 days vs. 15 days) compared to those administered with the thermal gel with the FVIII solution. The bioactivity of the released proteins remained at ≥90% of the native forms.Conclusions: Pre-encapsulation in dextran microparticles effectively mitigates burst release from thermosensitive hydrogels, while preserving protein functionality.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROBIOLOGY AND IMMUNOLOGY
·
2017
·Vol. 62
·期 3
·187-194
·
IF 1.706
Cenrong Zhang,Wei Xu,Jian Chen,Ran Guan,Shicheng Bi,Haibo Jin,Xuemei Cui,Fushan Shi,Songhua Hu
In the present study, the adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in serum and muscle tissue after intramuscular injection of SO-GS-R. The results showed that injection of SO-GS-R significantly increased the levels of IL-1β, IL-5, IL-6, G-CSF, KC, MCP-1, MIP-1α, and MIP-1β in both serum and muscle. These results suggested that SO-GS-R recruits neutrophils, eosinophils, T cells and macrophages, causing immune cell recruitment at the injection site, driving antigen-presenting cells to actively participate in the onset of immunity, and amplifying the immune responses. Considering its adjuvant activity and plant-derived properties, SO-GS-R should be further studied for its adjuvant effect on vaccines used in food animals.
研究领域:
免疫学
·
兽医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Xiang Yu,Lin Zhu,Xiaohui Liang,Bochuan Yuan,Minshu Li,Shen Hu,Pingtian Ding,Lina Du,Junwang Guo,Yiguang Jin
Exposure to a nuclear accident or a radiological attack may cause serious death events due to ionizing radiation-induced injury and acute radiation syndrome (ARS). Recombinant human granulocyte colony-stimulating factor (G-CSF) is now used for the treatment of ARS. However, the current injection formulation might not ensure treatment as early as possible after a nuclear accident, resulting in a decrease in therapeutic efficiency. In the present study, we have developed a G-CSF wearable system (GWS) consisting of a commercial microchip, a temperature sensor , a gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle (GTSMN) patch. G-CSF-containing hyaluronic acid solutions were cast into the mold to obtain G-CSF microneedles (GMNs), which were coated with a temperature-sensitive layer of dodecanoic acid-cetylamine salt to obtain GTSMNs. The flexible heater was prepared by jet printing Ag nanoparticle inks. The GWS and its components are explored and optimized in the aspects of electronics, mechanics, heat transfer and drug diffusion . The γ radiation signal is sensitively monitored by the GWS. The wearable G-CSF system immediately releases G-CSF into the body in response to signal feedback and provides maximal protection against ionizing radiation-induced injury. Therefore, the GWS is a promising wearable system against emergent ionizing radiation injury. Statement of significance Ionizing radiation-induced injury is always the very important public health problem all the global people care. Some medicines have been applied to protect the body from the injury. Unfortunately, sometimes the injuries accidently happen and the medicines cannot be administered in time, leading to serious acute radiation syndrome. Here, we design a wearable system loading G-CSF that has been approved by FDA to protect the body from ionizing radiation-induced injury. This system consists of a commercial microchip, a temperature sensor, a Gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle patch. It can monitor γ radiation and immediately release G-CSF into the body to protect the body to the maximal extent. Therefore, the system is a promising wearable medical device against emergent ionizing radiation injury.
研究领域:
生物医学工程
·
辐射防护
·
药物传递系统
·
材料科学
✓ 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）