1.Advances in research on biomaterials and stem cell/exosome-based strategies in the treatment of traumatic brain injury.
Wenya CHI ; Yingying HE ; Shuisheng CHEN ; Lingyi GUO ; Yan YUAN ; Rongjie LI ; Ruiyao LIU ; Dairan ZHOU ; Jianzhong DU ; Tao XU ; Yuan YU
Acta Pharmaceutica Sinica B 2025;15(7):3511-3544
Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.
2.Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.
Jianyu YAN ; Tianyu WANG ; Ruizhi YU ; Lijuan XU ; Hongming SHAO ; Tengfei LI ; Zhe WANG ; Xudong CHA ; Zhenyuan MIAO ; Chengguo XING ; Ke XU ; Huanhai LIU ; Chunlin ZHUANG
Acta Pharmaceutica Sinica B 2025;15(8):4137-4155
Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTACKEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTACKEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.
3.Discovery of fernane-type triterpenoids from Diaporthe discoidispora using genome mining and HSQC-based SMART technology.
Yajing WANG ; Yongfu LI ; Yan DONG ; Chunyan YU ; Chengwei LIU ; Chang LI ; Yi SUN ; Yuehu PEI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(3):368-376
In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification*
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Antifungal Agents/isolation & purification*
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Molecular Structure
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Candida albicans/drug effects*
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Ascomycota/genetics*
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Magnetic Resonance Spectroscopy
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Aspergillus niger/drug effects*
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Genome, Fungal
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Microbial Sensitivity Tests
4.Study on CMV-DNA detection in blood and urine
Like ZHANG ; Qianqian CHEN ; Xuegao YU ; Bin HUANG ; Jihong LIU ; Peisong CHEN
International Journal of Laboratory Medicine 2018;39(2):179-181
Objective To study the detection of cytomegalovirus (CMV)-DNA in different kinds of blood and urine sample .Methods The CMV-DNA loads in 3 different kinds of blood sample from 52 patients and 3 different kinds of urine sample from 85 patients were detected by real-time fluorescence quantitative polymer-ase chain reaction(FQ-PCR) .The differences in CMV-DNA detection rate and virus loads were compared a-mong different kinds of blood and urine samples .Results The CMV-DNA detection rates in serum ,whole blood ,plasma and peripheral blood mononuclear cell (PBMC) from 52 patients were 48 .08% ,71 .15% ,57 .69% and 69 .23% respectively .The CMV-DNA detection rates of whole blood and PBMC were higher ,the difference was statistically significant (P<0 .05) .The quantitative results of PBMC was higher .The CMV-DNA detec-tion rates of mixed urine ,urine supernatant and urine sediment from 85 patients were 72 .94% ,62 .35% and 84 .71% respectively ,the CMV-DNA detection rate of urine sediment was higher ,while the quantitative re-sults of mixed urine was higher .Conclusion The CMV-DNA detection results of blood and urine have large difference ,therefore using the same kind of sample for conducting detection has an important clinical signifi-cance in the clinical diagnosis ,treatment and monitoring of CM V infection .
5.Influence of orthokeratology lens on vision, intraocular pressure and biometric measurement parameters of adolescent myopia
Xiaobing WANG ; Like ZHANG ; Yinghong QIU ; Wenlin YU ; Hongyu YANG ; Bin XING ; Zhikai LI
Chongqing Medicine 2017;46(16):2204-2205,2208
Objective To evaluate the influence of orthokeratology lenses on vision,intraocular pressure and biometric measurement parameters in adolescent myopia.Methods A total of 72 adolescent myopia patients (136 eyes) with orthokeratology lens,aged 8-16 years old,in Hebei Provincial Eye Hospital from Junuary 2013 to December 2015 were randomly selected.The vision,intraocular pressure,axial length,corneal topography,corneal thickness and anterior chamber depth were observed before wearing glasses,at 1 week,1,3,6 months after wearing glasses.Results After orthokeratology wearing,the uncorrected visual acuity was obviously improved (P<0.05),the average refraction diopter was declined (P>0.05) and the non-contact intraocular pressure was decreased (P<0.05).The axial length after orthokeratology wearing had little change (P>0.05).The curvature of the patient's cornea at one week after wearing glasses was deceased (P<0.05) and the posterior corneal curvature tended towards stability.The corneal thickness at 1 week after wearing glasses had no obvious change compared with before wearing glasses(P>0.05),which at 1 month after wearing glasses was decreased(P<0.05) and which at 3,6 months after wearing glasses trended to be stabilized.The anterior chamber depth after wearing glasses had no obvious change.Conclusion Orthkeratology lens can decrease the myopia degree,increases the uncorrected visual acuity and has obvious effect for controlling adolescent myopia.The intraocular pressure and biometric measurement parameters have corresponding change after wearing orthkeratology lens.
6.Correlation of interaction between genetic polymorphisms with thrombin activity in plasma and pathological stages of esophageal carcinoma
Chaoxian ZHANG ; Like GUO ; Lili ZHANG ; Yu HAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(3):437-444
Objective To investigate the correlation of interaction between polymorphisms of prothrombin gene G20210A in 3' untranslated region and tissue factor pathway inhibitor (TFPI) gene C399T in 5' untranslated region with thrombin activity in plasma and the pathological stages of esophageal carcinoma.Methods Based on TNM method,we selected 198 patients with stage Ⅰ esophageal carcinoma,198 with stage Ⅱ,198 with stage Ⅲ,and 198 with stage Ⅳ from the First Affiliated Hospital of Xinxiang Medical College from May 2011 to August 2015 for this study;198 patients with esophageal carcinoma of stage 0 served as the control group.The thrombin activity in plasma were determined by chromogenic substrate assay.The genetic polymorphisms of prothrombin gene G20210A in 3' untranslated region and TFPI gene C399T in 5' untranslated region in peripheral blood leukocytes of the above-mentioned patients were analyzed by PCR-RFLP technique.Unconditional logistic regression model and single factor analysis were performed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of polymorphisms prothrombin gene G20210A and TFPI gene C399T polymorphisms and to analyze the interaction of nucleotide polymorphisms with thrombin activity in plasma and the pathological stages of esophageal carcinoma.Results The frequencies of G20210A (GA),G20210A (AA),C399T (CT) and C399T (TT) were 24.24%,26.77%,24.24% and 25.76% in stage Ⅰ group;34.34%,37.37%,34.85% and 36.36% in stage Ⅱ group;39.90%,42.93%,40.41% and 41.92% in stage Ⅲ group;45.45%,46.97%,45.35% and 46.46 in stage Ⅳ group;and 13.64%,14.14%,13.13% and 13.64% in stage 0 group,respectively.Statistical tests showed significant difference in the frequencies among each group (all P<0.01).The risks of invasion and metastasis of esophageal carcinoma significantly increased in the subjects with G20210A,in those with G20210A(AA) genotype,in those with C399T (CT) genotype and in those with C399T (TT) genotype.Combined analysis of the polymorphisms showed that percentage of G20210A (AA)/C399T (TT) in stage Ⅰ group,stage Ⅱ group,stage Ⅲ group,stage Ⅳ group and stage 0 group was 7.07%,14.14%,18.18%,21.71% and 1.52%,respectively,and statistical tests showed significant difference in the frequency among each group (all P<0.01).People who carried G20210A(AA)/C399T(TT) had higher risks of invasion and metastasis of esophageal carcinoma,and statistical analysis suggested a positive interaction between G20210A (AA) and C399T (TT) in increasing the risks of invasion and metastasis of esophageal carcinoma (All γ> 1).Likewise,there were also positive interactions in the pathogenesis of invasion and metastasis of esophageal carcinoma between G20210A (GA) and C399T (TT),G20210A (GA) and C399T(CT),G20210A (AA) and C399T (CT) (All γ>1).The thrombin activities in plasma in stage Ⅰ,Ⅱ,Ⅲ and Ⅳ groups were all significantly higher than those in stage 0 group,and there were significant differences among stage Ⅰ,stage Ⅱ,stage Ⅲ and stage Ⅳ in thrombin activities (all P<0.01).Patients with mutation genotype had significantly higher thrombin activities than those with wild homozygous in the same TNM stage.Conclusion G20210A and C399T gene mutations are the risk factors in the invasion and metastasis of esophageal carcinoma.Significant interactions between G20210A and C399T mutations increase the risk of invasion and metastasis of esophageal carcinoma,which may be closely related to their increased thrombin activities in plasma.
7.Clinical Observation of Salmeterol and Fluticasone Propionate in the Treatment of Moderate and Severe Bronchial Asthma
China Pharmacy 2016;27(23):3270-3272
OBJECTIVE:To observe clinical efficacy and safety of salmeterol and fluticasone propionate in the treatment of mod-erate and severe bronchial asthma. METHODS:98 patients with moderate and severe bronchial asthma were selected from our hospi-tal were included in the study and were randomly divided into control group(49 cases,3 cases withdrew from the test and 46 cases completed the test)and observation group(49 cases,2 cases withdrew from the test and 47 cases completed the test). Control group was given Budesonide aerosol preparation,1 dose,bid;observation group was given Salmeterol and fluticasone propionate inhala-tion,1 dose,bid. The treatment course lasted for 2 months. Clinical efficacy,lung function indexes,the time of clinical symptom disappearance,FEV1,PD20,ACT score,asthma attack times within half an year,EO%and ECP in serum and sputum,and the oc-currence of ADR were compared between 2 groups. RESULTS:After treatment,total effective rate of observation group was signifi-cantly higher than that of control group(95.73% vs. 76.09%);FVC,FEV1 and PEF and other indexes of 2 groups were increased significantly,and the observation group was significantly higher than the control group;the disappearance time of pulmonary rales, wheezing,dyspnea and cough in observation group were significantly shorter than in control group;PD20 and ACT score of 2 groups were significantly increased,ACT score of observation group was significantly higher than that of control group;EO% and ECP in serum and sputum of observation group were significantly lower than those of control group,there was statistical significance (P<0.05). Asthma attack times within half an year in observation was less than control group,there was no statistical significance (P>0.05). All ADRs disappeared after drug withdrawal. CONCLUSIONS:Therapeutic efficacy of salmeterol and fluticasone propio-nate is better than budesonide in the treatment of moderate and severe bronchial asthma,and can effectively improve lung function, shorten the time of clinical symptoms disapperance and reduce the level of inflammatory factor with and good safety.
8.Comparison of Efficacy and Safety of Rosuvastatin and Atorvastatin in the Treatment of Coronary Heart Dis-ease
China Pharmacy 2016;27(12):1611-1613
OBJECTIVE:To compare the efficacy and safety of rosuvastatin and atorvastatin in the treatment of coronary heart disease. METHODS:96 patients with coronary heart disease were randomly divided into observation group and control group. All patients received reasonable diet control,low molecular weight heparin,Aspirin enteric-coated tablet,β-blockers,nitric acid lipids and other conventional treatment,but no vitamins and other antioxidant drugs. Based on it,observation group was orally given 10 mg Rosuvastatin tablet,once a day;control group was given 20 mg Atorvastatin capsule,once a day. The treatment course for both groups was 6 months. Clinical efficacy, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol(HDL-C),high-sensitivity C-reactive protein(hs-CRP)and left ventricular ejection fraction (LVEF) before and after treatment,and the incidence of adverse reactions in 2 groups were observed. RESULTS:There were no significant differences in the total effective rate and incidence of adverse reactions between 2 groups(P>0.05). Before treat-ment,there were no significant differences in the TC,TG,LDL-C,HDL-C,hs-CRP and LVEF between 2 groups(P>0.05). After treatment,TC,TG,LDL-C,HDL-C and hs-CRP in 2 groups were significantly lower than before,and TC,LDL-C and hs-CRP in observation group were lower than control group,HDL-C and LVEF in 2 groups were significantly higher than before,and observa-tion group was higher than control group,the differences were statistically significant (P<0.05). CONCLUSIONS:Rosuvastatin and atorvastatin has similar efficacy and safety in the treatment of coronary heart disease,but rosuvastatin is superior to atorvastatin in terms of reducing lipid levels.
10.The detection of serum soluble B7-H4 levels in non-small cell lung cancer patients and its significance
Chunhua XU ; Like YU ; Qingbo WANG
Chinese Journal of Laboratory Medicine 2012;35(7):604-606
ObjectiveTo detect serum soluble B7-H4 (sB7-H4) levels in patients with non-small cell lung cancer ( NSCLC ) and explore its clinical significances.MethodsThe sB7-H4 levels the sera of in 102 NSCLC patients,60 benign lung disease patients and 90 healthy controls were determined by ELISA.The relation between serum sB7-H4 levels and NSCLC of pathological staging was analyzed by use of t test.ResultsThe serum sB7-H4 levels in NSCLC,benign lung disease and heathy control groups were (45.61 ±5.67 ),( 30.14 ± 3.51 ) and ( 28.52 ± 4.76 ) μg/L,respectively.The levels of NSCLC group were significantly higher than those of benign lung disease and healthy control groups ( t =2,59 and 3.61,P < 0.05 ).The serum sB7-H4 levels of Ⅲ/IV stage NSCLC patients ( 63.93 t 4.76 ) μgL,with lymph node metastasis (61.73 ±3.97) μg/L and before operation patients (63.29 ±6.19) μg/L were relatively higher thanthose inthe Ⅰ/Ⅱ stage(35.12 ± 3.88 )μg/L, without lymphnode metastasis (40.26 ± 5.39 ) μg/L,after operation ( 40.51± 4.08 ) μg/L.There were significant difference ( t =6.78,5.73 and 3.67,P < 0.05 ).Conclusions Serum sB7-H4 of NSCLC patients increases significantly and correlates with clinical stages and therapeutic conditions.Detecting on sB7-H4 is helpful for lung cancer diagnosis and therapeutic effect evaluation.

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