1.Advances in the study of polymeric micelles used in oral administration
Dong CHEN ; Pingtian DING ; Yihui DENG ; Siling WANG
Acta Pharmaceutica Sinica 2010;45(5):560-4
Polymeric micelles which are self-assembled from amphiphilic copolymers are thermodynamically stable, and they can solubilize hydrophobic drugs by the hydrophilic core. Many excellent active compounds are confined because of general low oral bioavailability due to poor solubility. Take into account from the two points above, polymeric micelles may be used as proper oral carrier to improve the dissolubility of hydrophobic drugs, and enhance the permeation though gastrointestinal tract, therefore, the pharmacodynamics is elevated. Meanwhile, the segments in copolymers are multivariate, so many kinds of micelles can be obtained, such as, pH- or thermo- sensitive as well as mucoadhesive ones. The modified micelles can alter drug release profiles while solubilizing them, that is why the oral bioavailability increase further. In this review, recent progress of polymeric micelles used in oral administration is summarized, and the prospect of polymeric micelles' application in this field is also evaluated.
2.Tumor-associated macrophages in immune microenvironment of lung cancer
Yihui DING ; Kai ZHANG ; Yue HU ; Li LIU
Journal of International Oncology 2014;41(11):830-833
With the research on tumor immunity and tumor immunosuppression development,immunotherapies for lung cancer has become a research hotspot.Tumor immune microenvironment plays an important role in tumor genesis,development and metastasis of lung cancer.Tumor-associated macrophages (TAMs) are the dominant leukocyte population found in immune microenvironment of lung cancer.The relationship between TAMs and lung cancer becomes clear with further research.TAMs may become the new target of lung cancer immunotherapy.
3.Effect and mechanism of IL-17 on heart failure in hypertensive rats
Yonggang DING ; Hongwu MA ; Jiaqi WEI ; Tiannan JIN ; Yihui LI ; Yingzi WANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(11):1343-1348
Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hy-pertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signa-ling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injec-tion group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injec-tion group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was estab-lished,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated pro-tein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P<0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P<0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P<0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P<0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P<0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)%vs(62.77±5.43)%,P<0.01].Conclusion IL-17/NF-κB/SERCA2 signaling pathway is involved in the regulation of inflammatory response after hypertensive HF,and inhibiting IL-17 can effective-ly improve the cardiac dysfunction caused by hypertensive HF.
4.Feasibility analysis of bone density evaluation with Hounsfield unit value after fibula flap reconstruction of jaw defect
Yihui YANG ; Yifan KANG ; Yifan YANG ; Mengkun DING ; Xiaofeng SHAN ; Zhigang CAI
Maxillofacial Plastic and Reconstructive Surgery 2023;45(1):30-
Background:
Implant-supported dentures have become an essential means of restoring occlusal function after jaw reconstruction. Bone mineral density (BMD) may influence the success rate of implant denture restorations. This study aimed to explore whether the Hounsfield unit (HU) value can be used to monitor the changing trend of fibular BMD after jaw reconstruction.
Results:
A total of 54 patients who underwent maxillar/mandibular reconstruction with a fibula flap were included in this study. There was a significant correlation between the HU value and BMD at 1 week, 3 months, and 6 months after surgery, and both were significantly correlated with follow-up time. The difference between each pair of absorption rates (DAR) was less than 10% in 66.7% and 75.9% of patients at 3 and 6 months; however, the DAR was more than 20% in 12% and 13.8% of patients at 3 and 6 months, respectively.
Conclusions
There is a significant correlation between HU value and BMD. The HU value can be used to roughly reflect the fibular BMD changing trend in a group of patients as opposed to an individual, and the HU value is not equivalent to BMD.
5.Effect of Polysaccharides and n-Butanol Fractions of Atractylodis Rhizoma Stir-fried with Bran on Metabonomics in Rats with Spleen Deficiency
Huiying XU ; Yihui DING ; Hao DONG ; Xuecen ZHAO ; Yang BAI ; Qian CAI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):112-120
ObjectiveTo explore the regulatory effect of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran on the plasma metabolites of spleen-deficient rats, and then to elucidate their mechanisms of spleen-enhancing effects. MethodForty male SD rats were randomly divided into the blank group, model group, polysaccharide group (FD group, 0.075 6 g·mL-1·d-1), n-butanol fractions group (FZ group, 0.012 1 g·mL-1·d-1), with 10 rats in each group. Except the blank group, the other three groups used the compound factors of overwork, dietary disorders and intragastric administration of Sennae Folium decoction to replicate the rat model of spleen deficiency. After the end of modeling, the FD group and FZ group were given the corresponding medicinal solution by gavage for 7 d, meanwhile, the blank group and model group were given an equal volume of saline. The plasma samples from rats in the blank, model, FZ and FD groups were analyzed by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS), multivariate statistical methods were used to process the data and screen differential metabolites, and metabolic pathway enrichment analysis of the screened differential metabolites was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG))database and MetaboAnalyst 5.0. ResultThe results of multivariate statistical analysis showed that there were significant differences in plasma metabolites between the model group and blank group, FZ group and model group, FD group and model group. There were 380 differential metabolites between the blank group and the model group, of which 78 and 57 were called back by polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran, respectively. Metabolic pathway enrichment results showed that the n-butanol fractions mainly affected glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, D-arginine and D-ornithine metabolism, which were summarized as amino acid metabolism, while the polysaccharides mainly affected glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, tricarboxylic acid cycle, biotin metabolism and thiamine metabolism. ConclusionBoth of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran have significant regulating effects on the metabolic abnormalities in spleen-deficient rats, in which the n-butanol fractions is mainly involved in amino acid metabolism, and the polysaccharides are involved in energy metabolism and cofactor and vitamin metabolism in addition to regulating amino acid metabolism.
6.Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis
Shaoxue DING ; Yihui ZHAO ; Ting WANG ; Jing GUAN ; Limin XING ; Hong LIU ; Guojin WANG ; Xiaoming WANG ; Yuhong WU ; Wen QU ; Jia SONG ; Huaquan WANG ; Lijuan LI ; Zonghong SHAO ; Rong FU
Chinese Journal of Hematology 2024;45(2):178-183
Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.
7.Management strategy of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis and a literature review
Yongjia HUANG ; Ling DING ; Fang ZENG ; Jie LIU ; Jindou LI ; Yihui LIU
China Pharmacy 2023;34(2):223-227
OBJECTIVE To provide reference for the management of antithrombotic therapy in thrombocytopenia patients with atrial fibrillation and atherosclerosis. METHODS The clinical pharmacist participated in the treatment of a thrombocytopenia patient with atrial fibrillation and atherosclerosis, and analyzed the causes of thrombocytopenia according to the patient’s medical history and laboratory examination results. At the same time, the risk of thrombosis-bleeding was evaluated according to the relevant guidelines, and the clinicians were assisted in formulating individual antithrombotic therapy plan and pharmaceutical care plan for the patient. The literature on antithrombotic therapy related to thrombocytopenia was collected and analyzed by retrieving CNKI. RESULTS Thrombocytopenia was considered as primary thrombocytopenia in this patient, and the main risk of bleeding was age ≥65 years old, bleeding tendency, and combined use of antithrombotic drugs. After the clinical pharmacist assessed the risk of thrombosis and bleeding, the clinician was recommended to give full dose of Bemiheparin sodium injection + Dronedarone hydrochloride tablets + Metoprolol succinate sustained-release tablets. In view of thrombocytopenia, the clinician gave Compound zaofan pill, Caffeic acid tablet and Sheng xuexiaoban capsule, but the patient developed diarrhea after the medication. The clinical pharmacist suggested stopping Sheng xuexiaoban capsule, and the clinician adopted the clinical pharmacist’s suggestion. When the patient was discharged from hospital, the clinical pharmacist suggested that the antithrombotic therapy plan for discharge was anticoagulation alone or selective anticoagulation. The clinician chose selective anticoagulation treatment considering that the patient’s current thrombocytopenia, urinary occult blood (+) and fecal occult blood were weakly positive, and ordered the patient to take Metoprolol succinate sustained-release tablets + Atorvastatin calcium tablets at discharge. Literature analysis showed that the causes of thrombocytopenia of patients with thromboembolism mainly included heparin induced-thrombocytopenia, immune thrombocytopenia, etc. All patients were improved after symptomatic treatment. CONCLUSIONS By participating in the management of antithrombotic therapy for the thrombocytopenia patient with atrial fibrillation and atherosclerosis, clinical pharmacists can help effectively control the patient’s condition and ensure the safety and effectiveness of drug use.
8.Sialic acid-mediated photochemotherapy enhances infiltration of CD8+ T cells from tumor-draining lymph nodes into tumors of immunosenescent mice.
Dezhi SUI ; Changzhi LI ; Xueying TANG ; Xianmin MENG ; Junqiang DING ; Qiongfen YANG ; Zhaowei QI ; Xinrong LIU ; Yihui DENG ; Yanzhi SONG
Acta Pharmaceutica Sinica B 2023;13(1):425-439
Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8+ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8+ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8+ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.
9.Urinary Metabolomics Aanlysis of Differences in Effect of Aconiti Coreani Radix and Typhonii Rhizoma on Gerbils with Stroke
Liting ZHOU ; Wanting ZENG ; Ru JIA ; Huiying XU ; Yihui DING ; Hao DONG ; Haowen MA ; Yang QU ; Qian CAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):157-166
ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique, and then to clarify the mechanism of the two, as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group(CG), model group(MG), Aconiti Coreani Radix group(RA) and Typhonii Rhizoma group(RT). Except for the CG, ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG, rats in the other groups received whole powder suspension(0.586 mg·g-1) was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0, 3, 7 and 14. After the end of administration, the serum, brain tissue and urine of gerbils in each group were collected, and the rate of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC), and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and nitric oxide(NO) in serum and brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), and the data were processed by multivariate statistical analysis, and differential metabolites were screened based on value of variable importance in the projection(VIP) of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG) database and Metaboanalyst 5.0. ResultCompared with the CG, the neurological deficit score was significantly increased in the MG(P<0.05), compared with the MG, the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d(P<0.05). Compared with the CG, the rate of cerebral infarction was significantly increased in the MG(P<0.05), compared with the MG, the rates of cerebral infarction in the RA and RT were significantly reduced(P<0.05). Compared with the CG, the levels of IL-6, TNF-α, and MDA in the serum and brain tissue of gerbils from the MG were significantly increased(P<0.05), and the levels of SOD, GSH and NO were significantly reduced(P<0.05). Compared with the MG, Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6, TNF-α and MDA, and up-regulated the levels of SOD, GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics, of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma, and could be used as potential biomarkers for both treatments in stroke gerbils, respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism, pyrimidine metabolism, and aminoacyl-tRNA biosynthesis. In addition, Aconiti Coreani Radix could also regulate riboflavin metabolism, Typhonii Rhizoma could also regulate purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of pantothenate and coenzyme A, and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke, with Aconiti Coreani Radix having stronger effects. From the metabolomics results, the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism, oxidative stress and so on, while Typhonii Rhizoma mainly involve amino acid metabolism, lipid metabolism, energy metabolism, etc.
10.Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma.
Xiyue ZHAO ; Xiaoyu LIU ; Pengcheng ZHANG ; Yiran LIU ; Wei RAN ; Ying CAI ; Junyang WANG ; Yihui ZHAI ; Guanru WANG ; Yaping DING ; Yaping LI
Acta Pharmaceutica Sinica B 2019;9(5):1050-1060
Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.