PHYTOMEDICINE
·
2024
·
IF 6.7
Wenxin Xia,Yushu Wang,Jiahui Yue,Xueyan Fu
Background Honey-fried Licorice (HFL) is a dosage form of Glycyrrhizae Radix et Rhizome processed with honey, which has been recorded to exhibit better efficacy in tonifying the spleen compared to the raw product. In contrast, different processing methods of Glycyrrhizae Radix et Rhizome exhibit different efficacies and applications, but their current quality control index components remain consistent. Purpose Based on the discovery and research strategy of traditional Chinese medicine decoction piece quality marker (Q-marker), this study aimed to conduct a multidimensional integration of constituents absorbed into the body and metabolomics based on the tonifying spleen and stomach effects of HFL to effectively identify the Q-marker of HFL. Methods In this study, a spleen deficiency rat model was established using the "exhausted swimming + poor diet" method to investigate the pharmacodynamics of tonifying the spleen and stomach by HFL. The constituents absorbed into blood was conducted using UPLC-Q-TOF/MS, correlation analysis between metabolomics and constituents absorbed into blood recognized the Q-Marker of HFL. Results The pharmacodynamic data demonstrated that HFL exhibited a significant regulatory effect on the disordered levels of PP, trypsin, chymase, PL, α-Glu, MTL, GAS, VIP, IL-2, IFN-γ, and IgA in the spleen deficiency model. Furthermore, HFL was found to improve the pathological changes in the spleen and intestine in the spleen deficiency model, highlighting its significant "tonifying spleen and stomach" effect. In the serum containing HFL, a total of 17 constituents were identified as being absorbed into the blood. Among these, 11 were prototypical components, while 6 were metabolites. Metabolomics data revealed that 9 differentially expressed metabolic markers were observed. Furthermore, the analysis of endogenous metabolic markers indicated that 10 components exhibited significant correlations with these biomarkers. Conclusion The effect of "tonifying spleen and stomach" of HFL is closely related to the regulation of the material and energy metabolism pathway. The Q-Marker of HFL is glycyrrhizic acid and 18 β -glycyrrhetinic acid as the main control standards and liquiritin, isoliquiritin, liquiritin, isoliquiritin, isolicorice flavonol, licorice chalcone C and Formononetin were used as auxiliary standards.
研究领域:
中药学
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药理学
·
代谢组学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Yuduo Gao,Luwei Zhang,Ziyue Wang,Hao Bai,Chengfan Wu,Qi Shuai,Yunfeng Yan
mRNA-based therapies hold tremendous promise for treating various diseases, yet their clinical success is hindered by delivery challenges. This study developed a library of 140 lipocationic Poly(β-amino ester)s (PBAEs) and formulated lipid-polymer hybrid nanoparticles (LPHs) with four helper lipids, including 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), to enhance mRNA delivery. Initial in vitro screening of four representative PBAEs identified the D/P4-1 formulation (DOTAP/PBAE molar ratio of 4:1) as the most effective. Further screening of the library using this formulation identified eight top-performing LPHs. In vivo experiments confirmed high luciferase expression in the spleen and lungs of mice following intravenous administration of Luc mRNA-loaded LPHs. Detailed analysis revealed that DOTAP incorporation influenced LPH properties, including apparent pKa, surface charge, and internal hydrophobicity, enabling enhanced mRNA release and cellular uptake. This study demonstrates potent approaches to modulate PBAE-lipid nanoparticle properties by altering PBAE structures and nanoparticle composition, offering insights for designing effective hybrid carriers for mRNA therapeutics.
研究领域:
药学
·
纳米技术
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2024
·Vol. 21
·期 1
·1-25
·
IF 9.3
Cheng Shimei,Lu Qiying,Liu Qiuli,Ma Yuanchen,Chen Jinshuo,Lu Di,Huang Mudan,Huang Yinong,Zhao Erming,Luo Jing,Zheng Haiqing
Background Neuronal death is the primary cause of poor outcomes in cerebral ischemia. The inflammatory infiltration in the early phase of ischemic stroke plays a vital role in triggering neuronal death. Either transplantation of mesenchymal stem cells (MSCs) derived from humans or repetitive transcranial magnetic stimulation (rTMS) have respectively proved to be neuroprotective and anti-inflammatory in cerebral ischemia. However, either treatment above has its limitations. Whether these two therapies have synergistic effects on improving neurological function and the underlying mechanisms remains unclear. This investigation aims to elucidate the synergistic effects and underlying mechanisms of MSCs combined with rTMS treatment on the neurological function recovery post-ischemia.Methods A Sprague-Dawley rat model of cerebral infarction was induced via transient middle cerebral artery occlusion (tMCAO). The rats were divided into five groups (n = 50): sham, tMCAO, rTMS, MSCs, and MSCs + rTMS groups. Transplantation of human umbilical cord MSCs and rTMS intervention were performed 24 h post-stroke. Neurological function was further assessed via several behavioral tests and the 2,3,5-triphenyltetrazolium chloride (TTC) staining companied with Nissl staining were used to assess neuronal survival. TUNEL staining, western blotting, immunofluorescence, immunohistochemistry, ELISA, and flow cytometry were employed to measure the levels of neuroinflammation and PANoptosis. The molecular mechanisms underlying the special role of rTMS in the combined therapy were distinguished with transcriptome sequencing via PC12 cells in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions.Results The combined therapy efficiently reduced lesion volume and improved neuronal survival (P < 0.05), subsequently improving functional recovery after ischemic stroke. MSCs + rTMS treatment ameliorated the PANoptosis in neurons (P < 0.05), accompanied by decreased levels of inflammatory factors in the cerebral tissue and serum during the subacute phase of cerebral infarction. To further explore the roles of either therapy on synergistic effect, we found that the transplanted MSCs primarily localized in the spleen and reduced cerebral inflammatory infiltration after ischemia via suppressed splenic inflammation. Meanwhile, rTMS significantly protects neurons from PANoptosis in MSCs-inhibited inflammatory conditions by downregulating REST unveiled by transcriptome sequencing.Conclusion sOur study elucidates an unidentified mechanism by which the combination of MSCs and rTMS could synergistically promote neuronal survival and suppress neuroinflammation during the subacute phase of cerebral infarction, thus improving neurological outcomes. The downregulating REST induced by rTMS may potentially contribute to the neuroprotective effect against PANoptosis in MSCs-inhibited inflammatory conditions. These results are expected to provide novel insights into the mechanisms of MSCs and rTMS combination therapy in synergistically protecting against cerebral ischemia injury and potential targets underlying neuronal PANoptosis in the early phase of stroke.
研究领域:
神经科学
·
干细胞生物学
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神经病学
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免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Qing Zhang,Yi Xu,Sheng Zou,Xiaodan Zhang,Kun Cao,Qi Fan
The alkali-extractable polysaccharides (APMPs) were isolated from the water extracted residues of Radix Polygoni Multiflori, and further purified by DEAE-52 cellulose and Sephadex G-100 column chromatography to obtain a homogeneous polysaccharide (APMP-2) with molecular weights of 7724.8 Da. HPLC chromatography analysis identified that APMP-2 was a heteropolysaccharides and mainly composed of Galactose and Xylose with a molar ratio of 4.31: 1.06. It was shown that both APMP and APMP-2 were of activation effects on splenocytes and peritoneal macrophages, and also significantly restore the proliferation rate, phagocytic index and cytokine (IL-2 and TNF-α) production level of 5-FU-treated splenocytes/peritoneal macrophages in a dosage-dependent manner. The results suggested that polysaccharides presented in Radix Polygoni Multiflori water-extracted residues possessed immunomodulatory activity and could be used as potential immunomodulators, and this finding could be a reference for the utilization of Radix Polygoni Multiflori water extracted residues.
研究领域:
药理学
·
免疫学
·
植物化学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2013
·
IF 2.632
Jing-En Li,Shao-Ping Nie,Ming-Yong Xie,Chang Li
A neutral polysaccharide MP-1 was isolated and purified from Mosla chinensis Maxim. cv. Jiangxiangru. The average molecular weight was 587.53 kDa and it was composed of glucose, galactose , arabinose , mannose and rhamnose in a molar ratio of 16.02:10.01:4.92:4.62:2.23, and trace of fucose . Partial characterization of MP-1 was elucidated by methylation analysis. MP-1 was composed of 1,4-Glc p (31.76%), followed by 1,2-Rha p (17.11%), 1,2,4-Rha p (6.47%), 1,3,4-Gal p (5.05%), 1,4-Man p (3.61%), 1,2,4-Man p (2.55%), 1,5-Ara f (3.10%) and 1,4,6-Glc p (1.53%). The branching points were located at O-2, O-4 or O-6 with α-Ara f (4.01%), α-Rha p (4.31%), α-Fuc p (2.39%), β-Gal p (11.02%) and β-Glc p (4.04%) as terminal residues. MP-1 exhibited a dose-dependent enhancement in antioxidant assays in this study. Immunomodulatory effects of MP-1 were assessed by splenocyte proliferation test and nitric oxide production of mouse peritoneal macrophages.
研究领域:
药理学
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免疫学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Lin Zhu,Mingming Zhang,Boyan Gao,Hong Zhang,Hai Zhang,Yaqiong Zhang,Liangli Lucy Yu
In this work, the paraffin oil was first molecularly distilled into two mineral oil saturated hydrocarbons (MOSH) subfractions with their main carbon number range of C20–30 (84.58%) and C30–50 (89.65%), which were determined using a liquid chromatography–gas chromatography–flame ionization detector (LC-GC-FID) technique. Then, both female and male Fischer 344 (F344) rats were fed with the diets containing one of these two MOSH subfractions at the low (1.5 g/kg) or high dose (15 g/kg) for 6 months. It was found that the exposure of MOSH C20–30 subfraction could result in a significant increase of spleen weight index (4.64 ± 0.18 mg/g for female and 3.79 ± 0.31 mg/g for male rats) (P < 0.05), and irregular shape of white medulla, and the macrophage infiltration in mesenteric lymph node for both female and male rats, especially for the 15 g/kg MOSH C20–30-fed rats. Meanwhile, both MOSH C20–30 and C30–50 subfraction promoted inflammation and oxidative stress and had a negative effect on the immune function in both female and male rats. The metabolomics results further supported these observations, and indicated the down-regulation of cysteine and methionine metabolism, and glutathione metabolism pathway in female and male rats, respectively.
研究领域:
毒理学
·
环境健康科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
·
免疫学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2016
·Vol. 9
·期 1
·334-340
·
IF 7.76
Meng Yang,Yanlei Liu,Wenxiu Hou,Xiao Zhi,Chunlei Zhang,Xinquan Jiang,Fei Pan,Yuming Yang,Jian Ni,Daxiang Cui
Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer. Our results showed that the tumor cells were efficiently killed by the heat generated from the gold nanorods, and the iPS cells ultimately died due to the action of MMC seven days after the photothermal treatment. This suggested that pre-treated iPS cells with MMC can be used as a novel and safe approach for targeted tumor therapy. This paves the road for clinical translation in the future.
研究领域:
生物医学工程
·
癌症研究
·
纳米技术
·
干细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Wenwen Zhou,Xiaoxiao Zhang,Meijuan Liu,Meiyu Wan,Shu Jiang,Erxin Shang,Jinao Duan
Guishao Yigong Decoction (GYD), a classic prescription that tonifies the spleen and qi, has been used in clinical practices for thousands of years to treat spleen deficiency. However, its in vitro and in vivo metabolic characteristics are still unclear. In this study, a rapid and reliable analytical method based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with automated data processing (MetaboLynx) was established to investigate the metabolites and metabolic pathways of GYD in vivo and in vitro . Based on the characteristics of protonated ions, eleven precursors (ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, atractylenolide I, atractylenolide III, paeoniflorin, glycyrrhizic acid, pachymic acid, liquiritin, nobiletin, and ferulic acid) and their corresponding metabolites were detected and tentatively identified. A total of 81 metabolites were identified, including 53 metabolites in vivo , 40 metabolites of liver microsomes, and 43 metabolites of intestinal flora in vitro . Distinct metabolic patterns were observed between intestinal flora and liver microsomes - the former primarily catalyzed phase I transformations (hydroxylation, methylation, dehydroxylation, demethylation, and reduction), while the latter also executed phase II metabolism, with glucuronidation being the predominant conjugation reaction. The metabolic profiling and pathways of active components in GYD were systematically analyzed, which was helpful in clarifying its potential mechanism and clinical application.
研究领域:
药理学
·
植物化学
·
代谢组学
·
中医药学
·
药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yu Han,Kai Zhang,Ning Xin,Xintao Gao,Guohua Ma,Jingtong An,Yantao Li
Despite recent advancements in lipid nanoparticles (LNPs)-based messenger RNA (mRNA) delivery, significant challenges persist in the structural optimization and functional modulation of their components for cancer immunotherapy, particularly regarding inadequate organ-specific targeting, and insufficient immune activation. Notably, metal ions have demonstrated emerging immunomodulatory potential, yet their coordinated self-assembly within LNPs as adjuvants to enhance the immunotherapeutic efficacy remains largely unexplored. To address these limitations, we combine newly designed imidazole-based LNPs with functional metal ions (Zn 2+ ) to develop novel Zn-coordinated LNP-based mRNA vaccines. A total of 48 imidazole-based ionizable lipids were designed and synthesized, among which C2–13 LNPs emerged as the top-performing formulation in terms of transfection efficiency. By innovatively incorporating Zn 2+ into C2–13 LNPs via coordination interaction, we further developed the novel metal-coordinated mRNA delivery systems, referred to as Zn-C2–13 LNPs. Compared to their non-metal counterparts, Zn-C2–13 LNPs exhibited markedly improved transfection efficiency and antigen presentation in vitro . Impressively, the synergistic effect of the optimized LNP formulation and Zn 2+ in the Zn-C2–13/mOVA systems (Zn-C2–13 LNPs loading ovalbumin mRNA) resulted in superior spleen-selective expression and immune response, significantly boosting the efficacy of cancer immunotherapy in the B16F10 ovalbumin-expressing (B16F10-OVA) melanoma tumor model. Collectively, this novel metal-coordinated LNPs improve specific organ targeting and immune responses, presenting a promising strategy to advance mRNA vaccine-based cancer immunotherapy.
研究领域:
免疫学
·
肿瘤学
·
纳米医学
·
分子生物学
·
转化医学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Xin-Ran Ge,Yi Zhao,Hao-Ran Ren,Fu-Wei Jiang,Shuo Liu,Ming Lou,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Jin-Long Li
As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment.
研究领域:
毒理学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Tianshi Li,Mengqi Shi,Yan Zhao,Zhongmei He,Ying Zong,Weijia Chen,Rui Du
As a traditional Chinese herbal medicine, Cornu Cervi Degelatinatum (CCD) has the effect of warming the kidney to support yang, astringing, and stopping bleeding, and is used for spleen kidney yang deficient (SKYD). This experiment was to investigate the therapeutic effects of different processes of CCD on SKYD type ulcerative colitis (UC) rats and to explore its impact on the intestinal flora of rats. Methods: ELISA was used to study the anti-inflammatory activity of Cornu Cervi Degelatinatum processed with water (WCCD) and Cornu Cervi Degelatinatum processed with vinegar (VCCD). 16SrRNA and transcriptome sequencing were used to detect the composition of rat intestinal flora and gene expression; RT-PCR and Western blot were used to verify the role of WCCD and VCCD in treating UC. Results: WCCD and VCCD have therapeutic effects on UC, could reduce tissue damage. VCCD performed better in improving Bacteroidetes/Firmicutes ratios and species evenness and abundance; performed better in increasing the quantity of lactobacillus. VCCD simultaneously inhibit the intestinal inflammatory response through NCK2, PAK4, and JNK signaling pathways. Conclusions: WCCD and VCCD play a therapeutic role in UC by regulating the proportion of different flora in the intestinal flora. VCCD regulates the intestinal flora and inflammatory response by interfering with the NCK2, PAK4 and JNK signaling pathways.
研究领域:
中医中药
·
药理学
·
分子生物学
·
胃肠病学
·
微生物学
✓ 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）