1.Application of Engineered Exosomes in Tumor-targeted Therapy
Jia-Lu SONG ; Yi-Xin JIN ; Xing-Yu MU ; Yu-Huan JIANG ; Jing WANG
Progress in Biochemistry and Biophysics 2025;52(5):1140-1151
		                        		
		                        			
		                        			Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine. 
		                        		
		                        		
		                        		
		                        	
2.Clinical effects of Modified Sanzi Yangqin Decoction combined with acupuncture on patients with chronic obstructive pulmonary disease at stable stage complicated with sarcopenia
Yan-Li ZHANG ; Yi-Xing SONG ; Dan XU
Chinese Traditional Patent Medicine 2024;46(1):107-111
		                        		
		                        			
		                        			AIM To explore the clinical effects of Modified Sanzi Yangqin Decoction combined with acupuncture on patients with chronic obstructive pulmonary disease at stable stage complicated with sarcopenia.METHODS Ninety-four patients were randomly assigned into control group(47 cases)for 8-week intervention of conventional treatment,and observation group(47 cases)for 8-week intervention of Modified Sanzi Yangqin Decoction,acupuncture and conventional treatment.The changes in clinical effects,TCM syndrome scores,and levels of pulmonary function indices(FVC,FEV1,FEV1/FVC),inflammatory factors(CRP,IL-6,TNF-α),muscle-specific biomarkers(MSTN,IGF-1),relevant scale scores(SARC-F,SPPB)and skeletal muscle mass index were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,inflammatory factors,MSTN,SARC-F score(P<0.05),and increased pulmonary function indices,IGF-1,SPPB score,skeletal muscle mass index(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with chronic obstructive pulmonary disease at stable stage complicated with sarcopenia,Modified Sanzi Yangqin Decoction combined with acupuncture exhibits significant clinical efficacy.
		                        		
		                        		
		                        		
		                        	
3.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
		                        		
		                        			 Objective:
		                        			To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). 
		                        		
		                        			Results:
		                        			A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). 
		                        		
		                        			Conclusion
		                        			The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value. 
		                        		
		                        		
		                        		
		                        	
4.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
		                        		
		                        			 Objective:
		                        			To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). 
		                        		
		                        			Results:
		                        			A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). 
		                        		
		                        			Conclusion
		                        			The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value. 
		                        		
		                        		
		                        		
		                        	
5.Hyperoside nanoparticles loaded with bone marrow mesenchymal stem cells synergistically repair endometrial injury
Rui-Fang HAN ; Hai-Yi ZHOU ; Xing-Shan LIANG ; Si-Yi HE ; Yong-Ge GUAN ; Yang SONG
Chinese Pharmacological Bulletin 2024;40(7):1302-1311
		                        		
		                        			
		                        			Aim To evaluate the effect of hyperoside/chitosan-nanoparticles(Hyp-NPs)on bone marrow mesenchymal stem cells(BMSCs)in vitro cell experi-ments and the underlying mechanism,and to conduct in vivo animal experiments to investigate the synergistic effect of Hyp-NPs and BMSCs on repairing endometrial damage in rats.Methods BMSCs were identified by flow cytometry.Hyp-NPs were prepared by ion crosslinking method,characterized and evaluated by laser particle size analyzer and transmission electron microscopy.The effects of different concentrations of Hyp-NPs on the migration of BMSCs were evaluated by scratch assay and immunofluorescence.NRF2 lentivir-us vector was constructed to explore the mechanism of Hyp-NPs on BMSCs.In animal experiments,Hyp-NPs loaded with BMSCs were co-transplanted into the uter-ine cavity of a rat model of endometrial injury.HE,Masson,IHC,TUNEL,and ELISA experiments were used to systematically evaluate the repair effect and pregnancy function of the composite formulation on rat endometrial injury from multiple aspects and angles,including general pathology,fibrosis,receptivity,cell proliferation,angiogenesis,stem cell recruitment,and inflammation of the endometrium.Results BMSCs were successfully isolated and cultured.Hyp-NPs with high stability and small particle size were successfully prepared.Scratch experiments indicated that Hyp-NPs could promote the migration of BMSCs.By successfully constructing a lentiviral NRF2 vector and oxidative damage model for BMSCs,immunofluorescence experi-ments showed that Hyp-NPs could regulate the biologi-cal axis of BMSCs by activating NRF2.Animal experi-ments showed that the synergistic administration of Hyp-NPs and BMSCs could increase endometrial thick-ness and glandular quantity,promote stem cell homing through anti-fibrotic,anti-apoptotic,and anti-inflam-matory effects,and restore pregnancy function in rats with endometrial injury.Conclusion The synergistic administration of Hyp-NPs and BMSCs could repair en-dometrial injury.
		                        		
		                        		
		                        		
		                        	
6.Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cra-nial Sutures in Northern Chinese Han Adults
Xuan WEI ; Yu-Shan CHEN ; Jie DING ; Chang-Xing SONG ; Jun-Jing WANG ; Zhao PENG ; Zhen-Hua DENG ; Xu YI ; Fei FAN
Journal of Forensic Medicine 2024;40(2):128-134,142
		                        		
		                        			
		                        			Objective To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation(MPR),and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population.Methods The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected.Volume reconstruction(VR)and MPR were performed on the skull,and 160 cranial suture tomography images were generated for each sample.Then the MPR images of cranial sutures were scored according to the closure grading criteria,and the mean closure grades of sagittal suture,coronal sutures(both left and right)and lambdoid sutures(both left and right)were calculated respectively.Finally taking the above grades as independent variables,the linear regression model and four machine learning models for age estimation(gradient boosting regression,support vector regression,decision tree regression and Bayesian ridge regression)were established for northern Chinese Han adults age estimation.The accu-racy of each model was evaluated.Results Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest.All four machine learning models had higher age estimation accuracy than linear regression model.The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years.Conclusion The combination of skull CT-MPR and machine learning model can be used for age esti-mation in northern Chinese Han adults,but it is still necessary to combine with other adult age estima-tion indicators in forensic practice.
		                        		
		                        		
		                        		
		                        	
7.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
		                        		
		                        			 Objective:
		                        			To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). 
		                        		
		                        			Results:
		                        			A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). 
		                        		
		                        			Conclusion
		                        			The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value. 
		                        		
		                        		
		                        		
		                        	
8.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
		                        		
		                        			 Objective:
		                        			To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). 
		                        		
		                        			Results:
		                        			A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). 
		                        		
		                        			Conclusion
		                        			The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value. 
		                        		
		                        		
		                        		
		                        	
9.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
		                        		
		                        			 Objective:
		                        			To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. 
		                        		
		                        			Methods:
		                        			A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). 
		                        		
		                        			Results:
		                        			A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). 
		                        		
		                        			Conclusion
		                        			The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value. 
		                        		
		                        		
		                        		
		                        	
10.Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine.
Xing DUAN ; Yi ZHANG ; Mengran GUO ; Na FAN ; Kepan CHEN ; Shugang QIN ; Wen XIAO ; Qian ZHENG ; Hai HUANG ; Xiawei WEI ; Yuquan WEI ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2023;13(3):942-954
		                        		
		                        			
		                        			The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.
		                        		
		                        		
		                        		
		                        	
            
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