JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Ranqi Yao,Wenqi Cui,Weidi Wang,Chenlu Feng,Ying Chen,Xiujuan Zhao
Perimenopausal depression is a subtype of depression that seriously harms women's health. The pathogenesis of perimenopausal depression remains unclear, which limits its prevention and therapy. Quercetin is a flavonoid with antidepressant and estrogen-like effects. This study aimed to explore the effects of quercetin on spleen metabolism in rats with perimenopausal depression and its potential mechanism. Untargeted metabolomics was employed to obtain splenic metabolite profiles, and 21 differential metabolites were identified. Pathway analysis revealed that glycerophospholipid metabolism, retinol metabolism, steroid hormone biosynthesis, and linoleic acid metabolism were disturbed. Notably, Spearman’s rank correlation analysis revealed that differential metabolites were significantly correlated with behavioral test results (p < 0.01). After treatment with quercetin, the intensities of the above differential metabolites were restored (p < 0.01), indicating that quercetin can improve the spleen metabolic disorder induced by the perimenopausal depression model. Further study showed that quercetin can increase the expression of PPAR-α in the hippocampus and spleen, reduce the expression of NF-κB and the levels of TNF-α and IL-6 in the spleen, and restore the expression of CREB and BDNF in the hippocampus (p < 0.05 or p < 0.01). Our study is the first to explore the effect of quercetin on spleen metabolism disorders in perimenopausal depression model rats using untargeted metabolomics. Quercetin can improve spleen metabolism disorders through multiple pathways, which may be related to the restoration of hippocampal neuroplasticity and reduction of spleen inflammation by regulating the brain-spleen axis. Our study provides a potential strategy for preventing and treating perimenopausal depression.
研究领域:
药理学
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神经科学
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代谢组学
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DOI
PubMed
高影响因子
INFLAMMATION
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2020
·Vol. 44
·期 2
·746-757
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IF 3.212
Gao Yang,Kang Kai,Liu Yan-song,Li Na-na,Han Qiu-yuan,Liu Hai-tao,Kong Wei-lan,Zhang Xing,Huang Rui,Yang Zhen-yu,Qi Zhi-dong,Zheng Jun-bo,Li Ming,Wang Hong-liang,Li Jia-yu,Liu Rui-jin,Wang Si-cong,Zhang Wei-hua,Zhao Ming-yan,Yu Kai-jiang
This study aimed to investigate the effect of splenectomy on dexmedetomidine-activated cholinergic anti-inflammatory pathway-mediated alleviation of LPS-induced AKI. A mouse model of septic kidney injury was established in C57BL/6 mice. A total of 30 C57BL/6 mice were randomly divided into the control group, LPS group, dexmedetomidine + LPS group, splenectomy group, splenectomy + LPS group, and splenectomy + dexmedetomidine + LPS group. The pathological effects in kidney tissues in each group were analyzed by HE staining. Apoptosis in each group was examined by the TUNEL method. Cr and Cys-C levels in each group were measured by ELISA. The expression levels of IL-6, NF-κB p65, Caspase-3, the antiapoptotic protein Bcl-2, the proapoptotic protein Bax, and α7nAChR in each group were measured by qRT-PCR and Western blotting. Dexmedetomidine alone reduced apoptosis in kidney tissue; however, apoptosis was increased after splenectomy in mice treated with dexmedetomidine. Splenectomy reduced the production of proinflammatory cytokines in circulation and had a protective effect on the kidney. Splenectomy inhibited dexmedetomidine-mediated activation of the α7nAChR pathway. Dexmedetomidine effectively alleviated LPS-induced kidney injury, and splenectomy inhibited the anti-inflammatory, antiapoptotic, and renoprotective effects of dexmedetomidine. The kidney-spleen axis is mediated by the α7nAChR-NF-κB signaling pathway and is involved in the development of AKI.
研究领域:
肾病学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2015
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IF 4.383
Dong Dong,Xiao Wang,Huailing Wang,Xingwang Zhang,Yifei Wang,Baojian Wu
Introduction SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals.Methods Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug’s disposition in rats following administration of drug cosolvent or nanocrystals.Results The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of −11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour).Conclusion The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.
研究领域:
药理学
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纳米医学
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肿瘤学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2019
·Vol. 20
·期 6
·1469
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IF 4.183
Xuerong Zhou,Ling Zhao,Jie Luo,Huaqiao Tang,Min Xu,Yanyan Wang,Xiaoyu Yang,Helin Chen,Yinglun Li,Gang Ye,Fei Shi,Cheng Lv,Bo Jing
Research has shown that nano-copper (nano-Cu) can cause damage to the spleen and immune system yet their mechanisms of cytotoxicity are poorly understood. Our aim is to explore the potential immunotoxicity in the spleen of rats after nano-Cu exposure. The results of hematologic parameters, lymphocyte subsets, immunoglobulins, and histopathology indicated that copper obviously changed the immune function of the spleen. The levels of antioxidants (SOD, CAT, GSH-Px), oxidants (iNOS, NO, MDA), and anti-oxidative signalling pathway of Nrf2 (Nrf2 and HO-1) were strongly induced by nano-Cu. The expression of mRNA and protein of pro-/anti-inflammatory (IFN-γ, TNF-α, MIP-1α, MCP-1, MIF, IL-1/-2/-4/-6) cytokines were increased by nano-Cu. The expression of regulatory signal pathways, MAPKs and PI3-K/Akt were activated, which might be involved in the inflammatory responses and immunomodulatory processes of sub-acute nano-Cu exposure. The immune function of the spleen was repressed by nano-Cu induced oxidative stress and inflammation.Keywords:nano-Cu;rats;spleen injury;immune system;oxidative stress
研究领域:
毒理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2022
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IF 4.966
Tianmeng Zhang,Zhuhua Dong,Feixue Liu,Enzhuang Pan,Nana He,Fenfen Ma,Xinyu Wu,Yan Wang,Jingquan Dong
Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms , has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 μg/L and 12.02 μg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration . Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-β1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress , inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.
研究领域:
水生生物学
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毒理学
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环境科学
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DOI
PubMed
高影响因子
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS
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2017
·Vol. 89
·期 1
·175-189
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IF 0.861
SHI CHEN-SHAN,SANG YA-XIN,SUN GUI-QING,LI TIAN-YE,GONG ZHENG-SI,WANG XIANG-HONG
Gracilariopsis lemaneiformis is a type of red alga that contains seaweed polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural analysis showed that GCP shows triple helical chain conformation when dissolved in water and has many branches and long side chains. Also, 1→3 linkage is the major linkage and the sugar structures are galactopyranose configurations linked by β-type glycosidic linkages. Two macromolecular substance fractions (GCP-1 and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography. Moreover, a splenocyte damage assay and splenocyte proliferation assay were used to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest protection rate, that is, 92.8%, which significantly enhanced the splenocyte proliferation, and GCP showed the highest proliferation rate, 9.30%. The results suggested that this type of novel non-agar polysaccharide displayed remarkable antioxidant and immunomodulatory activities and early alkali treatment could decrease the activities. It may represent a potential material for health food and clinical medicines.
研究领域:
海洋生物学
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生物化学
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免疫学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2014
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IF 3.916
Guoting Cui,Wuxia Zhang,Qingjie Wang,Amin Zhang,Haibo Mu,Hongjin Bai,Jinyou Duan
The versatile Fructus Jujubae is widely used in Chinese and Korean traditional medicine. In this study, the extraction optimization, characterization and immunostimulatory activities of polysaccharides from Fructus Jujubae were investigated. Based on a four-variable-three-level Box–Behnken statistical design, the optimal extraction parameters were optimized as follows: extraction temperature 90 °C, extraction time 3.23 h, water to raw material ratio 33:1 and extraction 3 times. Under these conditions, the experimental yield of polysaccharides was 6.47 ± 0.26%, which was close to the predicted yield value (6.54%). The crude Fructus Jujubae polysaccharide was further purified by DEAE-cellulose chromatography repeatedly, and two homogenous fractions, designated as RQP1d and RQP2d with molecular weight of 83.8 and 123.0 kDa respectively, were obtained. Their structures were determined by chemical analysis, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Finally, preliminary immunological tests indicated that both RQP1d and RQP2d significantly stimulated NO production in RAW264.7 macrophages, and promoted LPS-induced splenocyte proliferation. These data implied Fructus Jujubae polysaccharides had the potential to be explored as novel natural immunostimulant for using in functional foods or medicine.
研究领域:
中药学
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生物化学
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免疫学
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DOI
PubMed
高影响因子
Redox Biology
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2025
·
IF 11.9
Chuanlin Feng,Lei Zhang,Xiaoyuan Zhou,Shiyu Lu,Ruowen Guo,Chao Song,Xin Zhang
The magnetic properties of substances directly determine their response to an externally applied magnetic field, which are closely associated with magnetoreception, magnetic resonance imaging (MRI), and magnetic bioeffects. However, people understanding of the magnetic properties of living organisms remains limited. In this study, we utilized NRF2 (nuclear factor erythroid 2-related factor 2) deficiency mice to investigate the contribution of redox (oxidation–reduction) homeostasis, in which the key process is the transfer of electron, a direct target of magnetic field and origin of paramagnetism. Our results show that the NRF2 -/- mice exhibit significantly altered systemic redox state, accompanied by increased magnetic susceptibility, particularly in the liver and spleen. Further analyses reveal that the levels of paramagnetic reactive oxygen species (ROS) in these tissues are markedly elevated compared to wild-type mice. Moreover, the concentrations of Fe 2+ and Fe 3+ are significantly elevated in NRF2 -/- mice, which are directly correlated with the increased magnetic susceptibility. The disrupted redox balance in NRF2 -/- mice not only exacerbates oxidative stress and iron deposition, but also induces impairs to the liver and spleen. The findings highlight the combined effects of ROS and iron metabolism in driving magnetic susceptibility changes, providing valuable theoretical insights for further research into magnetic bioeffects effects and organ-specific sensitivity to magnetic fields.
研究领域:
生物物理学
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分子生物学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2025
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IF 2.8
Ruobing Bai,Liting Ma,Fangtong Li,Lijia Pan,Yuwen Bao,Xinze Li,Shen Wang,Hao Yue,Fei Zheng
For thousands of years, traditional Chinese medicine (TCM) has made extensive use of wild ginseng. It is thought to provide vital energy effects and to boost immunity. This study aimed to clarify the processes by which short-chain fatty acids (SCFAs) metabolites and the intestinal barrier are used by total ginsenosides wild ginseng (TWG) to modulate immunity. In this study, we analyzed and identified ginsenosides in the colon using UPLC-Q-TOF-MS E methods. In the meantime, a rat model of spleen qi deficiency (SQD) was created using reserpine, and the effects of TWG on intestinal barrier function and short-chain fatty acids in the feces of SQD-affected rats were examined. 28 ginsenosides were found in the colon during this experiment, and the main components were measured. TWG considerably increased fecal concentrations of acetic, propionic and 6 others, according to SCFAs analysis. According to serum immunological markers, TWG reduced IL-17 and IL-1β levels, increased IL-10, IL-22, and TGF-β concentrations, balanced Th17/Treg ratios, and reduced toxicants such DAO and LPS in rats with SQD. TWG improved barrier function, reduced permeability, increased tight junction protein expression, and lessened intestinal injury. A favorable correlation between intestinal barrier proteins and fatty acids was shown by correlation studies. The gut barrier and SCFAs perspectives helped to clarify the mechanism by which TWG controls immune activity. This study offers a fresh theoretical framework for TWG's future advancement and application.
研究领域:
中医药学
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免疫学
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胃肠病学
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微生物组研究
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Yichen Li,Yi Cao,Hao Bai,Luwei Zhang,Baiqiu Chen,Chengfan Wu,Qi Shuai,Yunfeng Yan
The application of mRNA-based therapies has gained significant attention in recent years, with lipid nanoparticles (LNPs) emerging as key delivery vehicles. However, challenges remain in optimizing delivery efficiency and targeting tissues beyond the liver, particularly for immunotherapy. In this study, we constructed novel lipids with disulfide bonds in the linkers and utilized the redox responsiveness of these bonds in the reductive microenvironment of tumor or immune cells to enable robust splenic mRNA delivery and potent cancer immunotherapy. A library of 119 lipids was synthesized by conjugating hydrophilic amines, disulfide-containing linkers, and hydrophobic amines via sequential aza-Michael addition. In vitro screening identified lipids with longer, branched hydrophobic tails, particularly 2C10, as leading carriers for mRNA delivery. Compared to conventional LNPs without disulfide linkers, disulfide-containing LNPs showed smaller size, higher mRNA binding, and enhanced mRNA release in the presence of GSH, with predominantly spleen-targeted in vivo delivery. Encapsulation with OVA mRNA promoted CD4 + and CD8 + T cell differentiation, leading to significant tumor regression in a melanoma mouse model. These findings highlight the potential of redox-responsive LNPs for targeted mRNA delivery and cancer immunotherapies.
研究领域:
生物技术
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药理学
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免疫学
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产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2021
·
IF 6.025
Rili Hao,Yang Jiang,Feng Li,Dongxiao Sun-Waterhouse,Dapeng Li
Cadmium (Cd) is a toxic heavy metal pollutant that can be accumulated in organs including the spleen, thereby threatening human health. In this study, the effect of caffeic acid phenethyl ester (CAPE, a bioactive component of honeybee propolis) on CdCl 2 -induced spleen toxicity and underlying mechanisms were examined in mice. Histological examinations revealed that CAPE (10 μmol/kg/day b.w.) could mitigate spleen damage induced by CdCl 2 (1.5 mg/kg/day b.w.) in mice. Compared to the mice treated only by CdCl 2 , CAPE administration increased the body weight while decreasing the spleen weight, spleen Cd content and spleen to body ratio of the CdCl 2 -treated mice. Western blot and ELISA tests revealed that CAPE suppressed CdCl 2 -induced inflammation (indicated by the decreases in the levels of inflammatory indictors). TUNEL and Western blot results showed that CAPE suppressed CdCl 2 -induced apoptosis through reducing the percentage of TUNEL-positive cells and regulating apoptosis factors. The antagonistic effect of CAPE against CdCl 2 -induced spleen toxicity was realized by increasing miR-182–5p expression to regulate the TLR4/NF-κB pathway. Therefore, CAPE could be a food-derived spleen protector to counteract Cd-induced spleen toxicity through alleviating apoptosis and inflammation via the miR-182–5p/TLR4/NF-κB axis.
研究领域:
毒理学
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药理学
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分子生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Lei Yan,Qin Zeng,Wenru Wang,Ying Liang,Rui Lang,Jingyi Zhan,Jiayi Yang,Renhuan Yu,Xinhui Wang
Ethnopharmacological relevance Jianpi Qushi Heluo formula (JQHF) is an evidence-based herbal formula based on "Fangji Huangqi Decoction" in the classic of traditional Chinese medicine (TCM) synopsis of the Golden Chamber. Its effectiveness in reducing idiopathic membranous nephropathy (IMN) proteinuria, edema and other clinical symptoms and improving kidney injury has been confirmed by clinical trials and animal experiments. These results demonstrate the critical significance of reducing podocyte injury by regulating mitophagy through integrating ethnopharmacology. Aim of the study This study aimed to explore the protective effects of JQHF on podocyte injury in IMN, focusing on its role in promoting PINK1-dependent mitophagy to inhibit reactive oxygen species (ROS) mediated activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Materials and Methods The main components of JQHF were identified by ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). Passive Heymann nephritis (PHN) was induced in rats using anti-Fx1A antiserum, while podocyte injury in vitro was stimulated with sublytic complement C5b-9 (sC5b-9). The PHN rats were treated with JQHF, and autophagy inhibitor 3-methyladenine (3-MA) combined with JQHF was used for pathway verification, and Benazepril served as a positive control. In vitro, podocytes were exposed to palmitic acid (PA, a ROS inducer) and N-acetylcysteine (NAC, a ROS scavenger). Further, we silenced the expression of PINK1 in podocytes model and intervened with JQHF-containing serum. Renal function was assessed through biochemical analyses and histopathology. Mitochondrial function was measured by detecting mitochondrial membrane potential (MMP), ROS levels as well as mitochondrial ultrastructure. The expression of podocyte structural proteins (desmin, nephrin, podocin) and inflammasome-related markers (NLRP3, caspase-1, IL-1β, IL-6) was analyzed to assess podocyte injury and inflammasome activation. Results (1) In vitro, in contrast to the control group, PA intervention caused increased ROS accumulation, reduced MMP, upregulated NLRP3 and caspase-1 expression, as well as elevated expression of inflammatory factors IL-1β and IL-6. The expression of nephrin and podocin was notably reduced. By contrast, NAC reversed these effects. (2) In vivo, JQHF effectively ameliorated mitochondrial damage, reduced NLRP3 expression and mitigated podocyte injury in PHN rats. The protective effects of JQHF were diminished by 3-MA, confirming the involvement of autophagy. (3) In vitro, JQHF-containing serum attenuated C5b-9-induced podocyte injury, improved mitochondrial dysfunction, and inhibited ROS-mediated activation of NLRP3 inflammasome. Silencing PINK1 significantly reversed these protective effects. Conclusion JQHF can alleviate podocyte damage, that through inhibiting ROS-mediated NLRP3 inflammasome activation by improving PINK1-mediated mitophagy.
研究领域:
免疫学
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分子生物学
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药理学
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转化医学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
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