1.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
2.Design, synthesis and evaluation of oxadiazoles as novel XO inhibitors
Hong-zhan WANG ; Ya-jun YANG ; Ying YANG ; Fei YE ; Jin-ying TIAN ; Chuan-ming ZHANG ; Zhi-yan XIAO
Acta Pharmaceutica Sinica 2025;60(1):164-171
Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor
3.Study on soluble microneedles loaded with aPexos and EGCG for healing of burn wounds in rats
Along ZHANG ; Wanjing LI ; Hong WANG ; Jiaxin LIU ; Ye CAO ; Rui ZHONG
Chinese Journal of Blood Transfusion 2025;38(3):333-342
[Objective] To use Chitosan Methacryloyl (CSMA) loaded with artificial platelet-derived exosomes (aPexos) as the needle body material, and gelatin and carboxymethyl chitosan (CMCS) loaded with Epigallocatechin gallate(EGCG) as the backing material to prepare microneedles, aims to investigate the therapeutic effect and mechanism of aPexos-EGCG microneedles in the treatment of burn wound healing. [Methods] First, aPexos were extracted using ultrasound and gradient ultracentrifugation. The concentration, morphology, and growth factor content (TGF-β1, PDGF-BB, VEGF) of the exosomes were assessed using NTA, transmission electron microscopy, and ELISA kits. The aPexos and EGCG were then dissolved in the needle body and backing materials, respectively. The aPexos and EGCG were loaded into the needle body and backing layer, respectively. The morphology, mechanical properties, and puncture performance of the microneedles were examined, and the preparation conditions for the microneedles loaded with aPexos-EGCG were optimized. Finally, animal experiments and tissue staining were conducted to assess the efficacy of the aPexos-EGCG microneedles in promoting burn wound healing in rats. [Results] The size distribution of aPexos was mainly in the range of 50-150 nm, with an average diameter of 132.7±3.8 nm and an average concentration of approximately 2.88×1013±3.62×1012 particles/mL. The concentrations of TGF-β1, PDGF-BB, and VEGF were approximately 1 363±135.9 ng/mL, 63.5±14.8 ng/mL, and 1 606.0±77.5 pg/mL, respectively. Mechanical property testing of the microneedles indicated that, compared with the blank microneedles, the drug-loaded microneedles had sufficient piercing ability to penetrate the stratum corneum of the skin. The results of the rat burn wound healing experiment showed that the wound healing rates of the d 3, d 7, aPexos-EGCG microneedle group compared to the control group showed significant differences, with respective values of (47.64±12.5)% vs (18.11±6.40)%, (87.45±5.57)% vs (79.85±5.03)%(P<0.05). Hematoxylin-eosin (HE) staining revealed more intact epidermal layers in the aPexos-EGCG microneedle group. Masson staining showed that the collagen deposition percentage in the aPexos-EGCG microneedle group was higher than in the control group. Immunofluorescence staining results indicated that the aPexos-EGCG microneedle group had a reduced content of M1-type macrophages and an increased content of M2-type macrophages. Additionally, the vascular markers CD31 and α-SMA showed elevated expression in this group, with significant differences compared to the other groups (P<0.05). [Conclusion] The aPexos-EGCG microneedle developed in this study exhibits good mechanical properties, capable of successfully penetrating the skin's stratum corneum and delivering aPexos and EGCG. aPexos promotes wound repair, while EGCG regulates the ratio of M1 and M2 macrophages at the wound site and suppresses the inflammatory response. This microneedle can effectively promote wound healing in rats with burn injuries, offering a novel approach for tissue repair.
4.Preparation and in vitro evaluation of platelet membrane biomimetic liposomes loaded with vincristine sulfate
Jing XIAO ; Xunyi YOU ; Along ZHANG ; Rui ZHONG ; Jiaxin LIU ; Ye CAO ; Hong WANG
Chinese Journal of Blood Transfusion 2025;38(5):652-659
Objective: To prepare platelet membrane biomimetic liposomes loaded with vincristine sulfate (VCR) for targeted delivery to tumor. Methods: Vincristine sulfate liposomes (LIPO) were prepared using the pH-gradient method, followed by the fusion of platelet membranes and subsequent drug loading to obtain platelet membrane biomimetic liposomes (PLM-LIPO). The particle size, polydispersity index (PDI), Zeta potential, and drug encapsulation efficiency (EE%) of both liposomes were characterized. The tumor-targeting capability was evaluated through in vitro cellular experiments and in vivo biodistribution studies. Results: The optimal preparation conditions for LIPO were determined as follows: DPPC-to-cholesterol molar ratio of 1∶1, internal aqueous phase of 0.3 M pH 4.0 citrate buffer, external aqueous phase of 1 M Na
HPO
solution, drug-to-lipid ratio of 1∶10, drug loading temperature of 60℃, and loading time of 10 minutes. The LIPO exhibited a mean particle size of (147.3±2.24) nm, PDI of 0.078±0.014, Zeta potential of (-3.54±0.75) mV, and EE% of 91.37±0.47. For PLM-LIPO, prepared via membrane fusion followed by drug loading, the mean particle size was (185.3±3.61) nm, PDI was 0.075±0.022, Zeta potential was (-18.91±1.54) mV, and EE% was 63.36±2.45. In the CD62P validation experiment, the fluorescence intensity of PLM-LIPO was five times higher than that of LIPO. In vitro cellular uptake experiments revealed that PLM-LIPO showed 1.3-fold and 1.2-fold higher uptake rates compared to LIPO at 6 h and 12 h, respectively. In vivo experiments demonstrated that 1h after administration, the accumulation of PLM-LIPO at tumor sites was 4-fold higher than that of LIPO and 6-7 times higher than that in healthy mice. Conclusion: The platelet membrane biomimetic liposomes loaded with vincristine sulfate were successfully developed. Both cellular uptake and tissue distribution studies confirmed the PLM-LIPO enhanced tumor-targeting capability.
5. Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway
Meng-Yu ZHANG ; Yan-Jie ZHENG ; Hong-Xia YE ; Chun-Hui WANG ; Yan-Li HU
Chinese Pharmacological Bulletin 2024;40(1):76-82
Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.
6.Virus spectrum of inpatients with acute respiratory infection in Pudong New Area , Shanghai
Zou CHEN ; Dan LIU ; Chuchu YE ; Hong ZHANG ; Qi ZHAO ; Lipeng HAO
Journal of Public Health and Preventive Medicine 2024;35(2):21-24
Objective To understand the viral spectrum of inpatients with acute respiratory infection in Pudong New Area, and to explore the composition of pathogens in hospitalized children and adults. Methods Samples of acute respiratory infection cases from 10 medical institutions were collected from 2011 to 2020 and tested for human influenza virus, human adenovirus, rhinovirus, human parainfluenza virus, respiratory syncytial virus, human coronavirus, human metapneumovirus and human boca virus. Results A total of 3 145 inpatients were monitored, with a median age of 61 years. The positive rate of any virus was 32.43% (1 020/3 145), and the single virus infection accounted for 85.98% (877/1 020). In single virus infection, the positive rate of human influenza virus was the highest (9.67%, 304/3 145), with influenza A (80.26%, 244/304) as the main virus. The second was rhinovirus (3.97%, 125/3 145). The positive rate of any virus in different age groups was statistically significant (χ2=103.38,P<0.001). The positive rate of respiratory syncytial virus was the highest in the ~5-year-old group, adenovirus was the highest in the 6-14-year-old group, and influenza virus was the highest in the 15-64-year-old group and the 65year-old group. There was a significant difference in the positive rate of any virus in each month (χ2=123.06,P<0.001). The human influenza virus was the dominant virus in winter (December to February) and summer (July to September), and rhinoviruses distributed sporadically in each month. The positive rate of any virus in different departments was significantly different (χ2=90.37,P<0.001). Conclusion The positive rate of virus in hospitalized patients with acute respiratory infection is relatively high in Pudong New Area, Shanghai, with human influenza virus being the main virus. The virus spectrum of hospitalized children and adults is inconsistent. In the future, in-depth research should be strengthened, focusing on the distribution of pathogens in different populations and seasonal prevention and treatment.
7.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
8.Recent advances in lamellar liquid crystal emulsification methods encapsulating natural active substances for functional cosmetics
Yi ZHANG ; Wei CHEN ; Yan-qi HAN ; Qian-wen SUN ; Yue GAO ; Jun YE ; Hong-liang WANG ; Li-li GAO ; Yu-ling LIU ; Yan-fang YANG
Acta Pharmaceutica Sinica 2024;59(2):350-358
Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.
9.Research progress on the stress-strain index of Corvis ST
International Eye Science 2024;24(1):97-100
Corneal visualization Scheimpflug technology(Corvis ST)is currently the most commonly used clinical device for assessing in vivo corneal biomechanics. The new parameter stress-strain index(SSI)has been a hot topic of clinical research in recent years, which not only directly reflect corneal biomaterial stiffness, but also closely correlates with the progression of certain diseases. SSI was generated based on the predictions of corneal behavior using finite element(FE)numerical modeling to simulate the effects of intraocular pressure and Corvis ST jets. The SSI algorithm does not change with central corneal thickness(CCT), intraocular pressure, or biomechanically corrected intraocular pressure(BIOP), but it is clearly associated with altered collagen fibres in the corneosclera. The principles of SSI, the relationship between age and SSI, the relationship between axial length and SSI, the relationship between myopia and SSI, and the application of SSI are summarized and concluded.
10.Rapid Analysis of Chemical Constituents in Shenxianshengmai Oral Liquid by UHPLC-Q Exactive Focus MS/MS
Shiyu ZONG ; Zhibiao DI ; Qiqi LIU ; Zhuangzhuang HUANG ; Hong ZHANG ; Ye LI ; Feng LIU ; Yang LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):218-228
Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.


Result Analysis
Print
Save
E-mail